Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1
Laura Doblado Bueno
 + 2988 word(s) 2988 2021-04-26 08:37:55 |
2 format change
Lily Guo
 Meta information modification 2988 2021-05-28 10:53:13 |

Video Upload Options

Do you have a full video?
Send video materials Upload full video

Confirm

Are you sure to Delete?
Yes No
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Doblado Bueno, L. Mitophagy. Encyclopedia. Available online: https://encyclopedia.pub/entry/10222 (accessed on 25 April 2024).
Doblado Bueno L. Mitophagy. Encyclopedia. Available at: https://encyclopedia.pub/entry/10222. Accessed April 25, 2024.
Doblado Bueno, Laura. "Mitophagy" Encyclopedia, https://encyclopedia.pub/entry/10222 (accessed April 25, 2024).
Doblado Bueno, L. (2021, May 28). Mitophagy. In Encyclopedia. https://encyclopedia.pub/entry/10222
Doblado Bueno, Laura. "Mitophagy." Encyclopedia. Web. 28 May, 2021.
Mitophagy
Edit
This entry is adapted from the peer-reviewed paper 10.3390/ijms22083903

Mitophagy is a selective autophagic process that eliminates unnecessary and/or damaged mitochondria. Therefore, it is a central hormetic mechanism of mitochondrial quality and quantity control, essential for cellular homeostasis. Its dysregulation has been shown to be a key event in metabolic related diseases and it is the target of emerging therapeutical approaches in this field.

Mitophagy parkin PINK1 autophagy human diseases

1. History

The capacity of the eukaryotic cell to regulate mitochondrial function provides the organisms with key metabolic plasticity, essential for a wide variety of cell functions [1][2]. Hence, maintenance of mitochondrial function relies on the adequate co-regulation of functions that control their turnover, namely mitochondrial biogenesis, which produces new mitochondria and mitophagy which eliminates damaged or unnecessary mitochondria [3]. Insufficient mitophagy leads to the accumulation of poorly functional/damaged mitochondria, with a reduced capacity to synthesize Adenosine triphosphate (ATP+), that produce high levels of superoxide. This can result in alteration in the cellular pools of intermediate metabolites, with pathological consequences [4]. Poorly functional mitochondria are a well-known hallmark of metabolic and neurodegenerative diseases, which are strongly linked to pathological developments. Alterations in the activity of key mitophagy regulators are central to these processes.

2. Mitophagy, a Type of Autophagy

It has to be highlighted that mitophagy is a type of selected autophagy [5]. Autophagy, literally “the process of the cell eating itself” in Greek, is divided into micro- or macro-autophagy, and chaperone-mediated autophagy, depending on the size of the degraded structure, and can be nonselective or selective, depending on whether any specific cellular component is targeted [6]. Of note, non-selective autophagy is emerging as a primary mechanism in cell death [7]. Early studies suggested that selective autophagy was closely related to (non-selective) macroautophagy, the only apparent difference being an additional step targeting isolation membranes to cargo. However, it has now been well established that, at least in yeast, several components of the canonical macroautophagy pathways are often dispensable for selective autophagy [8]. Therefore, mitophagy is a selective autophagy process that involves isolation within a membrane, sealing, and degradation through the lysosomal pathway of the organelle [9]. However, most subcellular structures, not just mitochondria, are targets of selective autophagy, including Golgi, the endoplasmic reticulum (ER), peroxisomes, ribosomes, the midbody, lipid droplets, and glycogen granules.
Mitophagy, defined as the selective autophagy of damaged mitochondria, was firstly described in yeast, where the presence of a mutated Uth1p in the outer mitochondrial membrane (OMM) was found to block autophagy during starvation [10]. Similar findings were later reported in cultured starved hepatocytes that eliminated damaged mitochondria when exposed to oxidative damage [11]. Commonly, the morphological characteristic feature of mitophagy is considered to be the localization of mitochondria inside an autophagic vacuole, called mitophagosomes [11][12]. However, currently, it is considered that there are three types of mitophagy: type 1, induced by nutrient limitation, type 2, induced by damage signals, and type 3, micro-mitophagy, linked to small mitochondria-derived vesicles [13]. These processes are intrinsically different, because type 1 and type 2 require the fusion of a lysosome to produce an autophagosome encircling mitochondria, while the latter type does not. Mitophagy plays a relevant role in normal development, as recently analyzed and quantified in vitro and in vivo in fluorescent transgenic mouse models (like mt-Keima or mito-QC) [14][15]. However, more generally, this fundamental biological mechanism works in all cells or tissues, being regulated in response to their changing energetic requirements. Some tissues, such as the nervous system, the kidney, the skeletal muscle, the heart, and the liver, show high basal mitophagy activity, while others, such as the spleen and the thymus, display low mitophagy levels[15][16]. The molecular and biochemical pathways involved in mitophagy were first characterized in models of aging [4], neurodegenerative and psychiatric diseases [17][18], cancer [18], and cardiovascular diseases (CVD) [19]. Basal mitophagy is, for example, vital to maintain synaptic plasticity and to eliminate damaged mitochondria in the brain, while its deranged activity is associated with age-related neuronal damage [20][21].

3. PINK1

Mitophagy can be phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase (PTEN)-induced putative kinase 1 (PINK1)-dependent or -independent [22]. PINK1 is a serine/threonine kinase whose levels are normally low, but it is stabilized and accumulates at the OMM in response to mitochondrial damage (mtDNA mutations), increased mitochondrial reactive oxygen species (ROS), depolarization, and the accumulation of misfolded proteins [23]. Accumulated PINK1 is autophosphorylated and activated, and in turn phosphorylates ubiquitin on serine 65, which recruits Parkin from the cytosol to the mitochondrial membrane. Parkin is an E3-ubiquitin ligase that, when recruited and activated, drives the ubiquitination of mitochondrial proteins and hence autophagy [24][25][26]. Recently, an inhibitory mechanism of the pathway has been described, and Ubiquitin carboxyl-terminal hydrolase 30 (USP30) can act as a brake on mitophagy by opposing Parkin-mediated ubiquitination [27]. Importantly, although PINK1 facilitates Parkin recruitment, Parkin can be recruited to depolarized mitochondria and drive mitophagy even in the absence of PINK1 [28]. Some identified targets of Parkin ligase activity at the OMM include Mitofusin 1 and 2 (MFN1/2), voltage dependent anion channel protein 1 (VDAC1), and mitochondrial Rho guanosine triphosphate hydrolases (GTPases) (MIRO) [28]. However, a widespread degradation of OMM has been evidenced by proteomic studies, suggesting that remodeling of the mitochondrial outer membrane proteome is important for mitophagy [26].
Under physiological steady state conditions, PINK1 is imported into the mitochondria through the translocase of the outer mitochondrial membrane (TOMM) complex of the OMM and into the translocase complex (TIMM) of the inner mitochondrial membrane (IMM), where it is cleaved by the mitochondrial processing peptidase (MPP) [29]. Afterwards, PINK1 is also cleaved in its hydrophobic domain, spanning the IMM, by the rhomboid protease presenilin-associated rhomboid-like protein (PARL), generating a 52 kD, N-terminal-deleted form of PINK1 [30]. PARL cleavage releases this PINK1 into the cytosol, where it is targeted by the N-degron type-2 E3 ubiquitin ligases and degraded by the ubiquitin proteasome system (UPS) [31]. This import and degradation cycle maintains PINK1 at very low, almost undetectable, levels on healthy mitochondria. However, mitochondrial import, through the TIMM complex, is affected by membrane depolarization, inhibition of the electron transport chain, genetic or environmental stressors, such as inflammation, and the accumulation of unfolded proteins. Under these adverse conditions, PINK1 processing by PARL is prevented, and uncleaved PINK1 accumulates on the OMM, bound to the TOMM complex [29]. This last event is needed to target PINK1 to selected single damaged mitochondrion [32].

4. Mitochondrial Homeostasis-Related Pathways

It should be highlighted that mitochondrial control through mitophagy is actually part of a more complex homeostatic control process of mitochondria that includes fusion and fission dynamics and mitochondrial biogenesis, with all these processes being interregulated [33]. Of note, mitochondrial fusion is induced upon starvation, and fused mitochondria are particularly resistant to mitophagy, while fragmented/fused organelles with low membrane potential (Δψm) are more easily targeted into mitophagosomes [34][35]. Accordingly, mitochondrial fusion/fission regulatory cues are also mitophagy modulators [36]. Other regulatory pathways still need to be fully characterized; for example, it has been suggested that mitophagy selectively targets certain mitochondria based on their topology. A recent study reported that serum-starved U2OS osteosarcoma cells formed “donut” mitochondria that exhibited normal inner membrane potential (Δψm) and were resistant to mitophagy, while swollen mitochondria with low potential were removed [37]. Mitophagy has also been shown to be regulated by changes in mitochondrial subcellular location and changes in cellular bioenergetics through regulators that control the main anabolic and catabolic pathways, as well as mitochondrial biogenesis [38].
Guanosine triphosphate hydrolases (GTPases) Mitofusin 1 and Mitofusin 2 (MFN1/2) are key players in the control of mitochondrial dynamics (fusion and fission) and orchestrate mitochondrial network connectivity and activity [39]. When mitochondria oxidative phosphorylation (OXPHOS) is activated, they fuse into a network that can cover the whole cell. Conversely, inhibition of mitochondrial OXPHOS activity is linked to the breakdown (fission) of the network into small mitochondrial units that tend to localize close to the nuclei. Fusion is induced by homo or hetero dimerization of MFN1/2, anchored to OMM at their C-termini, which mediate the GTP-dependent merge of separate OMMs. Fusion is also activated by MitoPLD, a member of the phospholipase D family, which converts, the mitochondrial-specific lipid cardiolipin (CL) into phosphatidic acid. CL is predominantly localized into the IMM, but mitochondrial damage leads to its relocalization to the OMM [40]. Fusion of the IMM and cristae organization requires full-length Optic Atrophy Protein 1 (L-OPA1). In cellular stress conditions, L-OPA1 is cleaved to S-OPA1, promoting OMM permeabilization and cytochrome c release [41]. The fission of mitochondrial OMM is also regulated by another GTPase protein, called dynamin-related protein 1 (Drp1) and its receptor proteins fission protein 1 (Fis1), mitochondrial fission factor (Mff) and mitochondrial dynamic proteins 49 and 51 kDa (MiD49 and MiD51) [42]. Intracellular signaling pathways regulate the positioning of Drp1 on the OMM. Once recruited, Drp1 oligomerizes into a ring-like structure that wraps around the mitochondria, which is also marked by the presence of endoplasmic reticulum (ER) and actin cytoskeleton, constricts the mitochondrial membrane and triggers fission [43].
Several related pathways have now been found to link mitochondrial dynamics to mitophagy, since damaged or unnecessary mitochondria should first be fused out and then degraded. In particular, MFN1/2 are extracted from the OMM by a ubiquitin-dependent chaperone and degraded by the proteasome [44]. Ubiquitination and depletion of MFN1/2 prevents the fusion of damaged mitochondria and leads to fragmentation, as fission processes remain functional, which promotes mitophagy [45]. PINK1 phosphorylates MFN2 that then works as a Parkin receptor for culling damaged mitochondria [46].
Although not a necessary element, voltage-dependent anion-selective channel 1 (VDAC1) also plays a relevant role in the control of mitophagy. VDAC1, the most abundant OMM protein, can be considered a mitochondrial porin. It largely controls mitochondrial permeability to a number of metabolites across the OMM and is a key regulatory element in mitochondria-dependent apoptosis [47]. It has been shown to interact with Parkin and become ubiquitinated and to be involved in Parkin recruitment. A recent study on VDAC1′s role in mitophagy revealed that Parkin can induce both mono- and polyubiquitination on VDAC1 [48]. Conversely, defective monoubiquitination leads to the induction of apoptosis, and reduced polyubiquitination hinders mitophagy, suggesting that VDAC1 interaction with Parkin is at a crossroads in terms of the decision to induce mitophagy or apoptosis by damaged mitochondria [49]. Of interest, another study identified an additional functional pathway of VDAC1 in mitophagy control through the cholesterol translocator protein (TSPO) [50]. TSPO facilitates the transfer of cholesterol from the OMM to the IMM, where it serves as a precursor for the synthesis of steroid hormones. It forms a functional complex with VDAC1 and has been shown that its overexpression inhibits mitophagy though an ROS-dependent mechanism that did not prevent the recruitment of Parkin but blocked the ubiquitination of mitochondrial proteins, though a still undefined mechanism.
Parkin also ubiquitinates the mitochondrial outer membrane Rho GTPases (MIRO1/2), which directly interact with PINK1 [51]. These proteins are components of the adaptor complex that anchors mitochondria to motor proteins. Thus, they are involved in the regulation of axonal mitochondrial movement by Ca2+ [52]. When Ca2+ binds, it causes the dissociation of motor/adaptor complexes from microtubules, thus leading to a mitochondrial movement arrest that facilitates the removal of damaged mitochondria by mitophagy [53]. MIRO serves as a Ca2+-dependent docking site and directly primes Parkin recruitment. However, the role of PINK1 and Parkin in MIRO1 degradation remains controversial. In fact, it has been proposed that MIRO1 ubiquitination, rather than its degradation, is the main signal for mitochondrial arrest [54].

5. LC3

Ubiquitination of the cargo is a critical step in selective autophagy in all cases [55]. The most accepted model is that cargo-bound receptors recruit microtubule-associated protein 1 light chain 3 (LC3) through an LC3-interacting region (LIR), bridging cargo with a preformed, autophagy-generated membrane. In this model, receptors are either integral to the cargo or recruited to the cargo via ubiquitination. A scaffold protein, which recruits additional autophagy-related proteins, may also be involved [56].
In mitochondria, following OMM remodeling mediated by proteasomal degradation of ubiquitinated proteins, adaptor proteins that bind ubiquitin (Ub) are recruited for the transport of depolarized mitochondria to the perinuclear region through a microtubule-dependent mechanism [57]. These adaptors interact with microtubule-associated protein 1 light chain 3 (LC3), which in turn promotes the sequestration of damaged mitochondria into autophagosomes. Finally, the autophagosomes fuse with the lysosomes, leading to the degradation of damaged mitochondria [5]. Five mitochondrial cargo-bound receptors (LC3 adapters) that contain an LIR motif that is recognized by LC3 [58] are recruited to the polyubiquitinated substrates on the mitochondria through their ubiquitin-binding domain: sequestosome-1 (p62), optineurin (OPTN), nuclear domain 10 protein 52 (NDP52), Trans-activating transcriptional regulatory protein of HTLV-1 (TAX1) binding protein 1 (TAX1BP1), and neighbor of Breast Cancer 1 (BRCA1) gene 1 (NBR1). Of note, it has been shown that OPTN [59] is largely dependent on its activation by Tank-binding kinase 1 (TBK1), a key signaling regulator of innate immunity, which highlights the interplay between mitophagy and the regulation of the immune system [60].

6. Ubiquitin Independent Mitophagy

It has been demonstrated that autophagy and mitophagy are upregulated in cells lacking PINK1 [61]. Damaged mitochondria can also be recognized by LC3 adapters in a ubiquitin-independent manner. These adapters directly sense mitochondrial damage and consequently change their subcellular location or the protein they interact with, guiding the damaged mitochondria to the autophagosome. The best characterized systems involved in the programmed mitochondrial clearance or mitochondrial elimination in the context of a developmental program are the B-Cell CLL/Lymphoma 2 (BCL2)/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3) and BCL2/adenovirus E1B 19 kDa-interacting protein 3-like (NIX/BNIP3L) pathways [62]. The current evidence suggests that both BNIP3 and NIX play an important role in oxygen sensing, inducing mitophagy in response to hypoxia, and can also directly promote the depolarization of mitochondria, as well as the fusion with cellular membranes. BIP3 and its homolog NIX are transmembrane OMM proteins. Their cytoplasmic N-terminal portion can interact with LC3-related molecules, targeting mitochondria for degradation by autophagy. BNIP3 is able to interact directly with PINK1, stabilizing it and promoting its ability to recruit Parkin, and its activity involves Drp1-mediated mitochondrial fission [63].
Other Parkin-independent mechanisms include those mediated by receptors, such as FUN14 domain-containing protein 1 (FUNDC1), another mitochondrial OMM protein sensitive to hypoxia [64]. Choline dehydrogenase (CHDH) is located in the IMM and OMM under normal conditions. When the mitochondrial membrane potential is disrupted, CHDH accumulates in the OMM and interacts with p62 through its Phox and Bem1 (PB1) domain, leading to the formation of the CHDH-p62-LC3 complex that mediates mitophagy [65]. TBC1 domain family member 15 (TBC1D15), a mitochondrial Rab GTPase activating protein, forms a complex with TBC1D17 and migrates to the mitochondrial outer membrane by interacting with Fis1. The TBC1D15/17 complex then interacts with LC3 [66]. Bcl2 like 13 (BCL2L13) is the mammalian homologue of Autophagy-related protein 32 Atg32, the only mitophagy receptor found in yeast [67]. Like other LC3 receptors, BCL2L13 locates on the OMM and binds to LC3 via the LC3-interacting region. FK506-binding protein 8 (FKBP8), located on the OMM, was identified as an LC3 interacting protein using yeast two-hybrid screening [68]. Remarkably, specific IMM components have also being shown to participate in mitophagy. Prohibitin 2 (PHB2) is a IMM protein [69] that becomes exposed to LC3 following Parkin-mediated degradation of OMM proteins. CL, as mentioned above, a membrane lipid in the IMM, can also function as an LC3 receptor in mitophagy when translocated from the IMM to the OMM in the presence of external depolarizing toxins [70]. Of note, the nutrient deprivation sensor, adenosine monophosphate activated protein kinase (AMPK), has also been shown to induce Parkin-independent mitophagy through the phosphorylation and activation of TBK1 [71].
The mitophagy main regulatory pathways have been summarized in Figure 1.
Ijms 22 03903 g001 550
Figure 1. Summary of main mitophagy pathways.

7. Novel Regulatory Pathways

Recent studies have also shown the physiological relevance of LC3-independent mitophagy. In particular, mitophagy can be driven by Rab9-associated autophagosomes, through the formation of a protein complex that involves Rab9, Unc-51-like kinase 1 (ULK1), and Drp1 [72].
Additional, novel pathways that impact mitophagy continue to be identified almost daily. For example, it has been demonstrated that, several ligases may regulate mitophagy, such as SMAD-specific E3 (SMURF1) [73], while the autophagy protein Coiled-coil myosin-like BCL2-interacting protein (BECN1)/Beclin 1, which plays a central role in autophagosome formation and maturation, has been shown to interact with Parkin and does not require its translocation to mitochondria [74].
Recently, a number of studies have focused on evidence linking mitophagy to ER stress, through the specialized ER-mitochondrial contact regions (MAMs) that regulate Ca2+ fluxes and control the induction of apoptosis [75]. PINK1 controls mitochondrial Ca2+ efflux [76][77], while, in turn, PINK1 gene expression has also been shown to be sensitive to Ca2+ fluxes [78]. The role of MAMS as key regulators of mitophagy is now well established, as they have been shown to be indispensable in the autophagy process, with many proteins that are directly involved in autophagy located in MAMs. In fact, in response mitophagy stimuli PINK1 and Beclin 1 have been shown to relocalize at MAMs where they further promote the association of mitochondria with ER, and autophagosome formation [79]. Although the mechanisms involved remain to be clearly elucidated [80], its physiological relevance has been clearly demonstrated, particularly in the context of Parkinson’s disease [81].

8. Implications for human diseases and therapeutical approaches

The central relevance of mitophagy in all diseases related to metabolic control is now well established. As mitophagy is required to control metabolic homeostasis or remove damaged or unnecessary mitochondria, it prevents mitochondrial malfunction and subsequent molecular events such as oxidative stress that lead to disease development. In diseased states, mitophagy can sometimes partially compensate other deficits alleviating them, but when mitochondrial activity is compromised, mitophagy can actually play a detrimental role. This is specially evidenced in diseases where normal mitophagy activity is compromised by genetic or regulatory events. These results have boosted pharmacological research in the field, since there are several potentially druggable targets along the mitophagy pathway. Some of these molecules are already showing promising results and more will certainly come soon. Several natural dietary compounds, such as polyphenols, flavonoids, spermidine, or trehalose, which restore normal mitophagy fluxes in the elderly [82][83], could help to control the inflammasome and to prevent neurodegeneration having a direct impact on apoptosis and the caspase activation cascade [84][85]. Perhaps more importantly, lifestyle interventions can promote cardiovascular health, boosting mitophagy [86][87]. The future could also bring new findings on novel, non-canonical mechanisms of mitochondrial quality control, such as the recently described mitochondrion-derived vesicles, characterized in hypoxic neurons and cardiomyocytes [88].

References

  1. Inmaculada Martínez-Reyes; Navdeep S. Chandel; Mitochondrial TCA cycle metabolites control physiology and disease. Nature Communications 2020, 11, 1-11, 10.1038/s41467-019-13668-3.
  2. John J. Lemasters; Selective Mitochondrial Autophagy, or Mitophagy, as a Targeted Defense Against Oxidative Stress, Mitochondrial Dysfunction, and Aging. Rejuvenation Research 2005, 8, 3-5, 10.1089/rej.2005.8.3.
  3. Insil Kim; Sara Rodriguez-Enriquez; John J. Lemasters; Selective degradation of mitochondria by mitophagy. Archives of Biochemistry and Biophysics 2007, 462, 245-253, 10.1016/j.abb.2007.03.034.
  4. Daniela Bakula; Morten Scheibye-Knudsen; MitophAging: Mitophagy in Aging and Disease. Frontiers in Cell and Developmental Biology 2020, 8, 239, 10.3389/fcell.2020.00239.
  5. Sarah Pickles; Pierre Vigié; Richard J. Youle; Mitophagy and Quality Control Mechanisms in Mitochondrial Maintenance. Current Biology 2018, 28, R170-R185, 10.1016/j.cub.2018.01.004.
  6. Damian Gatica; Vikramjit Lahiri; Daniel J. Klionsky; Cargo recognition and degradation by selective autophagy. Nature 2018, 20, 233-242, 10.1038/s41556-018-0037-z.
  7. Seonghee Jung; Hyeonjeong Jeong; Seong-Woon Yu; Autophagy as a decisive process for cell death. Experimental & Molecular Medicine 2020, 52, 921-930, 10.1038/s12276-020-0455-4.
  8. Tomotake Kanki; Daniel J. Klionsky; Mitophagy in Yeast Occurs through a Selective Mechanism. Journal of Biological Chemistry 2008, 283, 32386-32393, 10.1074/jbc.m802403200.
  9. Kei Okatsu; Keiko Saisho; Midori Shimanuki; Kazuto Nakada; Hiroshi Shitara; Yu-Shin Sou; Mayumi Kimura; Shigeto Sato; Nobutaka Hattori; Masaaki Komatsu; et al.Keiji TanakaNoriyuki Matsuda p62/SQSTM1 cooperates with Parkin for perinuclear clustering of depolarized mitochondria. Genes to Cells 2010, 15, 887-900, 10.1111/j.1365-2443.2010.01426.x.
  10. Konstantinos Palikaras; Eirini Lionaki; Nektarios Tavernarakis; Mechanisms of mitophagy in cellular homeostasis, physiology and pathology. Nature 2018, 20, 1013-1022, 10.1038/s41556-018-0176-2.
  11. Maria Zachari; Nicholas T. Ktistakis; Mammalian Mitophagosome Formation: A Focus on the Early Signals and Steps. Frontiers in Cell and Developmental Biology 2020, 8, 171, 10.3389/fcell.2020.00171.
  12. Thomas G. McWilliams; Alan R. Prescott; Lambert Montava-Garriga; Graeme Ball; François Singh; Erica Barini; Miratul M.K. Muqit; Simon P. Brooks; Ian G. Ganley; Basal Mitophagy Occurs Independently of PINK1 in Mouse Tissues of High Metabolic Demand. Cell Metabolism 2018, 27, 439-449.e5, 10.1016/j.cmet.2017.12.008.
  13. John J. Lemasters; Variants of mitochondrial autophagy: Types 1 and 2 mitophagy and micromitophagy (Type 3). Redox Biology 2014, 2, 749-754, 10.1016/j.redox.2014.06.004.
  14. Jee-Hyun Um; Young Yeon Kim; Toren Finkel; Jeanho Yun; Sensitive Measurement of Mitophagy by Flow Cytometry Using the pH-dependent Fluorescent Reporter mt-Keima. Journal of Visualized Experiments 2018, -, 58099, 10.3791/58099.
  15. Nuo Sun; Jeanho Yun; Jie Liu; Daniela Malide; Chengyu Liu; Ilsa I. Rovira; Kira M. Holmström; Maria M. Fergusson; Young Hyun Yoo; Christian A. Combs; et al.Toren Finkel Measuring In Vivo Mitophagy. Molecular Cell 2015, 60, 685-696, 10.1016/j.molcel.2015.10.009.
  16. Nadia Cummins; Jürgen Götz; Shedding light on mitophagy in neurons: what is the evidence for PINK1/Parkin mitophagy in vivo?. Cellular and Molecular Life Sciences 2017, 75, 1151-1162, 10.1007/s00018-017-2692-9.
  17. Yurong Zhang; Mengdi Zhang; Wei Zhu; Jie Yu; Qiaoyun Wang; Jinjin Zhang; Yaru Cui; Xiaohong Pan; Xue Gao; Hongliu Sun; et al. Succinate accumulation induces mitochondrial reactive oxygen species generation and promotes status epilepticus in the kainic acid rat model. Redox Biology 2020, 28, 101365, 10.1016/j.redox.2019.101365.
  18. J P Bernardini; M Lazarou; G Dewson; Parkin and mitophagy in cancer. Oncogene 2016, 36, 1315-1327, 10.1038/onc.2016.302.
  19. Jose Manuel Bravo-San Pedro; Guido Kroemer; Lorenzo Galluzzi; Autophagy and Mitophagy in Cardiovascular Disease. Circulation Research 2017, 120, 1812-1824, 10.1161/circresaha.117.311082.
  20. Konstantinos Palikaras; Nektarios Tavernarakis; Regulation and roles of mitophagy at synapses. Mechanisms of Ageing and Development 2020, 187, 111216, 10.1016/j.mad.2020.111216.
  21. Alfonso Schiavi; Flavie Strappazzon; Natascia Ventura; Mitophagy and iron: two actors sharing the stage in age-associated neuronal pathologies. Mechanisms of Ageing and Development 2020, 188, 111252, 10.1016/j.mad.2020.111252.
  22. Akinori Eiyama; Koji Okamoto; PINK1/Parkin-mediated mitophagy in mammalian cells. Current Opinion in Cell Biology 2015, 33, 95-101, 10.1016/j.ceb.2015.01.002.
  23. Shiori Sekine; PINK1 import regulation at a crossroad of mitochondrial fate.. The Journal of Biochemistry 2019, 167, 217-224, 10.1093/jb/mvz069.
  24. Derek Narendra; Atsushi Tanaka; Der-Fen Suen; Richard J. Youle; Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. Journal of Cell Biology 2008, 183, 795-803, 10.1083/jcb.200809125.
  25. Noriyuki Matsuda; Phospho-ubiquitin: upending the PINK–Parkin–ubiquitin cascade. The Journal of Biochemistry 2016, 159, 379-385, 10.1093/jb/mvv125.
  26. Nickie C. Chan; Anna M. Salazar; Anh H. Pham; Michael J. Sweredoski; Natalie J. Kolawa; Robert L.J. Graham; Sonja Hess; David C. Chan; Broad activation of the ubiquitin–proteasome system by Parkin is critical for mitophagy. Human Molecular Genetics 2011, 20, 1726-1737, 10.1093/hmg/ddr048.
  27. Baris Bingol; Morgan Sheng; Mechanisms of mitophagy: PINK1, Parkin, USP30 and beyond. Free Radical Biology and Medicine 2016, 100, 210-222, 10.1016/j.freeradbiomed.2016.04.015.
  28. Hong-Min Ni; Jessica A. Williams; Wen-Xing Ding; Mitochondrial dynamics and mitochondrial quality control. Redox Biology 2015, 4, 6-13, 10.1016/j.redox.2014.11.006.
  29. Michael Lazarou; Seok Min Jin; Lesley A. Kane; Richard J. Youle; Role of PINK1 Binding to the TOM Complex and Alternate Intracellular Membranes in Recruitment and Activation of the E3 Ligase Parkin. Developmental Cell 2012, 22, 320-333, 10.1016/j.devcel.2011.12.014.
  30. Emma Deas; Helene Plun-Favreau; Sonia Gandhi; Howard Desmond; Svend Kjaer; Samantha H.Y. Loh; Alan E. Renton; Robert J. Harvey; Alexander J. Whitworth; L. Miguel Martins; et al.Andrey AbramovNicholas W. Wood PINK1 cleavage at position A103 by the mitochondrial protease PARL. Human Molecular Genetics 2010, 20, 867-879, 10.1093/hmg/ddq526.
  31. Koji Yamano; Richard J Youle; PINK1 is degraded through the N-end rule pathway. Autophagy 2013, 9, 1758-1769, 10.4161/auto.24633.
  32. Alicia Pickrell; Richard J. Youle; The Roles of PINK1, Parkin, and Mitochondrial Fidelity in Parkinson’s Disease. Neuron 2015, 85, 257-273, 10.1016/j.neuron.2014.12.007.
  33. Verónica Eisner; Martin Picard; György Hajnóczky; Mitochondrial dynamics in adaptive and maladaptive cellular stress responses. Nature 2018, 20, 755-765, 10.1038/s41556-018-0133-0.
  34. Angelika S. Rambold; Brenda Kostelecky; Natalie Elia; Jennifer Lippincott-Schwartz; Tubular network formation protects mitochondria from autophagosomal degradation during nutrient starvation. Proceedings of the National Academy of Sciences 2011, 108, 10190-10195, 10.1073/pnas.1107402108.
  35. Ligia C. Gomes; Giulietta Di Benedetto; Luca Scorrano; During autophagy mitochondria elongate, are spared from degradation and sustain cell viability. Nature 2011, 13, 589-598, 10.1038/ncb2220.
  36. Laura M. Westrate; Jeffrey A. Drocco; Katie R. Martin; William S. Hlavacek; Jeffrey P. MacKeigan; Mitochondrial Morphological Features Are Associated with Fission and Fusion Events. PLOS ONE 2014, 9, e95265, 10.1371/journal.pone.0095265.
  37. YanShuang Zhou; Qi Long; Xingguo Liu; A new sight: topology-dependent mitophagy. Cell Biology and Toxicology 2020, 36, 199-204, 10.1007/s10565-020-09534-4.
  38. Pablo E. Morales; Carla Arias-Durán; Yáreni Ávalos-Guajardo; Geraldine Aedo; Hugo E. Verdejo; Valentina Parra; Sergio Lavandero; Emerging role of mitophagy in cardiovascular physiology and pathology. Molecular Aspects of Medicine 2020, 71, 100822, 10.1016/j.mam.2019.09.006.
  39. Prashant Mishra; David C. Chan; Metabolic regulation of mitochondrial dynamics. Journal of Cell Biology 2016, 212, 379-387, 10.1083/jcb.201511036.
  40. Jan Dudek; Role of Cardiolipin in Mitochondrial Signaling Pathways. Frontiers in Cell and Developmental Biology 2017, 5, 90-90, 10.3389/fcell.2017.00090.
  41. Seungyoon B. Yu; Gulcin Pekkurnaz; Mechanisms Orchestrating Mitochondrial Dynamics for Energy Homeostasis. Journal of Molecular Biology 2018, 430, 3922-3941, 10.1016/j.jmb.2018.07.027.
  42. Oliver C. Losón; Zhiyin Song; Hsiuchen Chen; David C. Chan; Fis1, Mff, MiD49, and MiD51 mediate Drp1 recruitment in mitochondrial fission. Molecular Biology of the Cell 2013, 24, 659-667, 10.1091/mbc.e12-10-0721.
  43. Jonathan R. Friedman; Laura L. Lackner; Matthew West; Jared R. DiBenedetto; Jodi Nunnari; Gia K. Voeltz; ER Tubules Mark Sites of Mitochondrial Division. Science 2011, 334, 358-362, 10.1126/science.1207385.
  44. Mafalda Escobar-Henriques; Mariana Joaquim; Mitofusins: Disease Gatekeepers and Hubs in Mitochondrial Quality Control by E3 Ligases. Frontiers in Physiology 2019, 10, 517, 10.3389/fphys.2019.00517.
  45. Atsushi Tanaka; Megan M. Cleland; Shan Xu; Derek P. Narendra; Der-Fen Suen; Mariusz Karbowski; Richard J. Youle; Proteasome and p97 mediate mitophagy and degradation of mitofusins induced by Parkin. Journal of Cell Biology 2010, 191, 1367-1380, 10.1083/jcb.201007013.
  46. Yun Chen; Gerald W. Dorn Ii; PINK1-Phosphorylated Mitofusin 2 Is a Parkin Receptor for Culling Damaged Mitochondria. Science 2013, 340, 471-475, 10.1126/science.1231031.
  47. Amadou K. S. Camara; Yifan Zhou; Po-Chao Wen; Emad Tajkhorshid; Wai-Meng Kwok; Mitochondrial VDAC1: A Key Gatekeeper as Potential Therapeutic Target. Frontiers in Physiology 2017, 8, 460, 10.3389/fphys.2017.00460.
  48. Sven Geisler; Kira M. Holmström; Diana Skujat; Fabienne C. Fiesel; Oliver C. Rothfuss; Philipp J. Kahle; Wolfdieter Springer; PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1. Nature 2010, 12, 119-131, 10.1038/ncb2012.
  49. Su Jin Ham; Daewon Lee; Heesuk Yoo; Kyoungho Jun; Heejin Shin; Jongkyeong Chung; Decision between mitophagy and apoptosis by Parkin via VDAC1 ubiquitination. Proceedings of the National Academy of Sciences 2020, 117, 4281-4291, 10.1073/pnas.1909814117.
  50. Jemma Gatliff; Daniel East; James Crosby; Rosella Abeti; Robert Harvey; William Craigen; Peter Parker; Michelangelo Campanella; TSPO interacts with VDAC1 and triggers a ROS-mediated inhibition of mitochondrial quality control. Autophagy 2014, 10, 2279-2296, 10.4161/15548627.2014.991665.
  51. Xinnan Wang; Dominic Winter; Ghazaleh Ashrafi; Julia Schlehe; Yao Liang Wong; Dennis Selkoe; Sarah Rice; Judith Steen; Matthew J. LaVoie; Thomas L. Schwarz; et al. PINK1 and Parkin Target Miro for Phosphorylation and Degradation to Arrest Mitochondrial Motility. Cell 2011, 147, 893-906, 10.1016/j.cell.2011.10.018.
  52. Lucia Barazzuol; Flavia Giamogante; Marisa Brini; Tito Calì; PINK1/Parkin Mediated Mitophagy, Ca2+ Signalling, and ER–Mitochondria Contacts in Parkinson’s Disease. International Journal of Molecular Sciences 2020, 21, 1772, 10.3390/ijms21051772.
  53. Xinnan Wang; Thomas L. Schwarz; The Mechanism of Ca2+-Dependent Regulation of Kinesin-Mediated Mitochondrial Motility. Cell 2009, 136, 163-174, 10.1016/j.cell.2008.11.046.
  54. Dzhamilja Safiulina; Malle Kuum; Vinay Choubey; Nana Gogichaishvili; Joanna Liiv; Miriam A Hickey; Michal Cagalinec; Merle Mandel; Akbar Zeb; Mailis Liiv; et al.Allen Kaasik Miro proteins prime mitochondria for Parkin translocation and mitophagy. The EMBO Journal 2018, 38, e99384, 10.15252/embj.201899384.
  55. Paul A. Ney; Mitochondrial autophagy: Origins, significance, and role of BNIP3 and NIX. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 2015, 1853, 2775-2783, 10.1016/j.bbamcr.2015.02.022.
  56. Terje Johansen; Trond Lamark; Selective Autophagy: ATG8 Family Proteins, LIR Motifs and Cargo Receptors. Journal of Molecular Biology 2020, 432, 80-103, 10.1016/j.jmb.2019.07.016.
  57. Michael Lazarou; Danielle A. Sliter; Lesley A. Kane; Shireen Sarraf; Chunxin Wang; Jonathon L. Burman; Dionisia P. Sideris; Adam I. Fogel; Richard J. Youle; The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy. Nature 2015, 524, 309-314, 10.1038/nature14893.
  58. Saori R. Yoshii; Noboru Mizushima; Autophagy machinery in the context of mammalian mitophagy. Biochimica et Biophysica Acta (BBA) - Bioenergetics 2015, 1853, 2797-2801, 10.1016/j.bbamcr.2015.01.013.
  59. Benjamin Richter; Danielle A. Sliter; Lina Herhaus; Alexandra Stolz; Chunxin Wang; Petra Beli; Gabriele Zaffagnini; Philipp Wild; Sascha Martens; Sebastian A. Wagner; et al.Richard J. YouleIvan Dikic Phosphorylation of OPTN by TBK1 enhances its binding to Ub chains and promotes selective autophagy of damaged mitochondria. Proceedings of the National Academy of Sciences 2016, 113, 4039-4044, 10.1073/pnas.1523926113.
  60. Andrew S. Moore; Erika L. F. Holzbaur; Dynamic recruitment and activation of ALS-associated TBK1 with its target optineurin are required for efficient mitophagy. Proceedings of the National Academy of Sciences 2016, 113, E3349-E3358, 10.1073/pnas.1523810113.
  61. Rubén Gómez-Sánchez; Sokhna M S Yakhine-Diop; José M Bravo-San Pedro; Elisa Pizarro-Estrella; Mario Rodríguez-Arribas; Vicente Climent; Francisco E Martin-Cano; María E González-Soltero; Anurag Tandon; José M Fuentes; et al.Rosa A González-Polo PINK1 deficiency enhances autophagy and mitophagy induction. Molecular & Cellular Oncology 2015, 3, e1046579, 10.1080/23723556.2015.1046579.
  62. J Zhang; P A Ney; Role of BNIP3 and NIX in cell death, autophagy, and mitophagy. Cell Death & Differentiation 2009, 16, 939-946, 10.1038/cdd.2009.16.
  63. Chengyuan Tang; Hailong Han; Zhiwen Liu; Yuxue Liu; Lijun Yin; Juan Cai; Liyu He; Yu Liu; Guochun Chen; Zhuohua Zhang; et al.Xiao-Ming YinZheng Dong Activation of BNIP3-mediated mitophagy protects against renal ischemia–reperfusion injury. Cell Death & Disease 2019, 10, 1-15, 10.1038/s41419-019-1899-0.
  64. Lei Liu; Du Feng; Guo Chen; Ming Chen; Qiaoxia Zheng; Pingping Song; Qi Ma; Chongzhuo Zhu; Rui Wang; Wanjun Qi; et al.Lei HuangPeng XueBaowei LiXiaohui WangHaijing JinJun WangFuquan YangPingsheng LiuYushan ZhuSenfang SuiQuan Chen Mitochondrial outer-membrane protein FUNDC1 mediates hypoxia-induced mitophagy in mammalian cells. Nature 2012, 14, 177-185, 10.1038/ncb2422.
  65. Sungwoo Park; Seon-Guk Choi; Seung-Min Yoo; Jin H Son; Yong-Keun Jung; Choline dehydrogenase interacts with SQSTM1/p62 to recruit LC3 and stimulate mitophagy. Autophagy 2014, 10, 1906-1920, 10.4161/auto.32177.
  66. Koji Yamano; Adam I Fogel; Chunxin Wang; Alexander M Van Der Bliek; Richard J Youle; Mitochondrial Rab GAPs govern autophagosome biogenesis during mitophagy. eLife 2014, 3, e01612, 10.7554/elife.01612.
  67. Xue Xia; Sarah Katzenell; Erin F. Reinhart; Katherine M. Bauer; Maria Pellegrini; Michael J. Ragusa; A pseudo-receiver domain in Atg32 is required for mitophagy. Autophagy 2018, 14, 1620-1628, 10.1080/15548627.2018.1472838.
  68. Zambarlal Bhujabal; Åsa B Birgisdottir; Eva Sjøttem; Hanne B Brenne; Aud Øvervatn; Sabrina Habisov; Vladimir Kirkin; Trond Lamark; Terje Johansen; FKBP8 recruits LC3A to mediate Parkin‐independent mitophagy. EMBO reports 2017, 18, 947-961, 10.15252/embr.201643147.
  69. Yongjie Wei; Wei-Chung Chiang; Rhea Sumpter; Prashant Mishra; Beth Levine; Prohibitin 2 Is an Inner Mitochondrial Membrane Mitophagy Receptor. Cell 2017, 168, 224-238.e10, 10.1016/j.cell.2016.11.042.
  70. Charleen Chu; Jing Ji; Ruben K. Dagda; Jian Fei Jiang; Yulia Tyurina; Oleksandr Kapralov; Vladimir A. Tyurin; Naveena Yanamala; Indira H. Shrivastava; Dariush Mohammadyani; et al.Kent Zhi Qiang WangJianhui ZhuJudith Klein-SeetharamanKrishnakumar BalasubramanianAndrew AmoscatoGrigory BorisenkoZhentai HuangAaron M. GusdonAmin CheikhiErin K. SteerRuth WangCatherine BatySimon WatkinsIvet BaharHülya BayırValerian E. Kagan Cardiolipin externalization to the outer mitochondrial membrane acts as an elimination signal for mitophagy in neuronal cells. Nature 2013, 15, 1197-1205, 10.1038/ncb2837.
  71. Alex P. Seabright; Nicholas H. F. Fine; Jonathan P. Barlow; Samuel O. Lord; Ibrahim Musa; Alexander Gray; Jack A. Bryant; Manuel Banzhaf; Gareth G. Lavery; D. Grahame Hardie; et al.David J. HodsonAndrew PhilpYu‐Chiang Lai AMPK activation induces mitophagy and promotes mitochondrial fission while activating TBK1 in a PINK1‐Parkin independent manner. The FASEB Journal 2020, 34, 6284-6301, 10.1096/fj.201903051r.
  72. Toshiro Saito; Jihoon Nah; Shin-Ichi Oka; Risa Mukai; Yoshiya Monden; Yasuhiro Maejima; Yoshiyuki Ikeda; Sebastiano Sciarretta; Tong Liu; Hong Li; et al.Erdene BaljinnyamDiego FraidenraichLuke FritzkyPeiyong ZhaiShizuko IchinoseMitsuaki IsobeChiao-Po HsuMondira KunduJunichi Sadoshima An alternative mitophagy pathway mediated by Rab9 protects the heart against ischemia. Journal of Clinical Investigation 2019, 129, 802-819, 10.1172/jci122035.
  73. Ersheng Kuang; Jianfei Qi; Ze’Ev Ronai; Emerging roles of E3 ubiquitin ligases in autophagy. Trends in Biochemical Sciences 2013, 38, 453-460, 10.1016/j.tibs.2013.06.008.
  74. Vinay Choubey; Michal Cagalinec; Joanna Liiv; Dzhamilja Safiulina; Miriam Hickey; Malle Kuum; Mailis Liiv; Tahira Anwar; Eeva-Liisa Eskelinen; Allen Kaasik; et al. BECN1 is involved in the initiation of mitophagy. Autophagy 2014, 10, 1105-1119, 10.4161/auto.28615.
  75. Maria Zachari; Sigurdur R. Gudmundsson; Ziyue Li; Maria Manifava; Fiorella Cugliandolo; Ronak Shah; Matthew Smith; James Stronge; Eleftherios Karanasios; Caterina Piunti; et al.Chieko Kishi-ItakuraHelena VihinenEija JokitaloJun-Lin GuanFolma BussAndrew M. SmithSimon A. WalkerEeva-Liisa EskelinenNicholas T. Ktistakis Selective Autophagy of Mitochondria on a Ubiquitin-Endoplasmic-Reticulum Platform. Developmental Cell 2019, 50, 627-643.e5, 10.1016/j.devcel.2019.06.016.
  76. Sonia Gandhi; Alison Wood-Kaczmar; Zhi Yao; Helene Plun-Favreau; Emma Deas; Kristina Klupsch; Julian Downward; David S. Latchman; Sarah Tabrizi; Nicholas W. Wood; et al.Michael DuchenAndrey Y. Abramov PINK1-Associated Parkinson's Disease Is Caused by Neuronal Vulnerability to Calcium-Induced Cell Death. Molecular Cell 2009, 33, 627-638, 10.1016/j.molcel.2009.02.013.
  77. Bavo Heeman; Chris Van Den Haute; Sarah-Ann Aelvoet; Federica Valsecchi; Richard J. Rodenburg; Veerle Reumers; Zeger Debyser; Geert Callewaert; Werner J. H. Koopman; Peter H. G. M. Willems; et al.Veerle Baekelandt Depletion of PINK1 affects mitochondrial metabolism, calcium homeostasis and energy maintenance. Journal of Cell Science 2011, 124, 1115-1125, 10.1242/jcs.078303.
  78. Rubén Gómez-Sánchez; Matthew E. Gegg; Jose Manuel Bravo-San Pedro; Mireia Niso-Santano; Lydia Alvarez-Erviti; Elisa Pizarro-Estrella; Yolanda Gutiérrez-Martín; Alberto Alvarez-Barrientos; José M. Fuentes; Rosa Ana González-Polo; et al.Anthony H.V. Schapira Mitochondrial impairment increases FL-PINK1 levels by calcium-dependent gene expression. Neurobiology of Disease 2014, 62, 426-440, 10.1016/j.nbd.2013.10.021.
  79. Vania Gelmetti; Priscilla De Rosa; Liliana Torosantucci; Elettra Sara Marini; Alessandra Romagnoli; Martina Di Rienzo; Giuseppe Arena; Domenico Vignone; Gian Maria Fimia; Enza Maria Valente; et al. PINK1 and BECN1 relocalize at mitochondria-associated membranes during mitophagy and promote ER-mitochondria tethering and autophagosome formation. Autophagy 2017, 13, 654-669, 10.1080/15548627.2016.1277309.
  80. Ming Yang; Chenrui Li; Shikun Yang; Ying Xiao; Xiaofen Xiong; Wei Chen; Hao Zhao; Qin Zhang; Yachun Han; Lin Sun; et al. Mitochondria-Associated ER Membranes – The Origin Site of Autophagy. Frontiers in Cell and Developmental Biology 2020, 8, 595, 10.3389/fcell.2020.00595.
  81. Junyang Jung; Youngbuhm Huh; Ulfuara Shefa; Na Young Jeong; In Ok Song; Hyung-Joo Chung; Dokyoung Kim; Mitophagy links oxidative stress conditions and neurodegenerative diseases. Neural Regeneration Research 2019, 14, 749-756, 10.4103/1673-5374.249218.
  82. Alessandra Stacchiotti; Giovanni Corsetti; Natural Compounds and Autophagy: Allies Against Neurodegeneration. Frontiers in Cell and Developmental Biology 2020, 8, 555409, 10.3389/fcell.2020.555409.
  83. Nimmy Varghese; Selina Werner; Amandine Grimm; Anne Eckert; Dietary Mitophagy Enhancer: A Strategy for Healthy Brain Aging?. Antioxidants 2020, 9, 932, 10.3390/antiox9100932.
  84. Yan Zhao; Shaohui Huang; Jie Liu; Ximing Wu; Shuai Zhou; Ke Dai; Yurong Kou; Mitophagy Contributes to the Pathogenesis of Inflammatory Diseases. Inflammation 2018, 41, 1590-1600, 10.1007/s10753-018-0835-2.
  85. Jae-Min Yuk; Prashanta Silwal; Eun-Kyeong Jo; Inflammasome and Mitophagy Connection in Health and Disease. International Journal of Molecular Sciences 2020, 21, 4714, 10.3390/ijms21134714.
  86. Giampaolo Morciano; Simone Patergnani; Massimo Bonora; Gaia Pedriali; Anna Tarocco; Esmaa Bouhamida; Saverio Marchi; Gina Ancora; Gabriele Anania; Mariusz R. Wieckowski; et al.Carlotta GiorgiPaolo Pinton Mitophagy in Cardiovascular Diseases. Journal of Clinical Medicine 2020, 9, 892, 10.3390/jcm9030892.
  87. Ne N. Wu; Haili Tian; Peijie Chen; Dan Wang; Jun Ren; Yingmei Zhang; Physical Exercise and Selective Autophagy: Benefit and Risk on Cardiovascular Health. Cells 2019, 8, 1436, 10.3390/cells8111436.
  88. Binghu Li; Hongliang Zhao; Yue Wu; Yu Zhu; Jie Zhang; Guangming Yang; Qingguang Yan; Junxia Li; Tao Li; Liangming Liu; et al. Mitochondrial-Derived Vesicles Protect Cardiomyocytes Against Hypoxic Damage. Frontiers in Cell and Developmental Biology 2020, 8, 214, 10.3389/fcell.2020.00214.
  89. Ne N. Wu; Haili Tian; Peijie Chen; Dan Wang; Jun Ren; Yingmei Zhang; Physical Exercise and Selective Autophagy: Benefit and Risk on Cardiovascular Health. Cells 2019, 8, 1436, 10.3390/cells8111436.
  90. Binghu Li; Hongliang Zhao; Yue Wu; Yu Zhu; Jie Zhang; Guangming Yang; Qingguang Yan; Junxia Li; Tao Li; Liangming Liu; et al. Mitochondrial-Derived Vesicles Protect Cardiomyocytes Against Hypoxic Damage. Frontiers in Cell and Developmental Biology 2020, 8, 214, 10.3389/fcell.2020.00214.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
Upload a video for this entry
Information
Subjects: Cell Biology
Contributor MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Laura Doblado Bueno
View Times: 903
Revisions: 2 times (View History)
Update Date: 28 May 2021
Table of Contents
    1000/1000
    Hot Most Recent
    Feedback