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Wen, X.; Tang, L.; Zhong, R.; Liu, L.; Chen, L.; Zhang, H. Role of Mitophagy in Regulating Intestinal Oxidative Damage. Encyclopedia. Available online: https://encyclopedia.pub/entry/41461 (accessed on 21 December 2024).
Wen X, Tang L, Zhong R, Liu L, Chen L, Zhang H. Role of Mitophagy in Regulating Intestinal Oxidative Damage. Encyclopedia. Available at: https://encyclopedia.pub/entry/41461. Accessed December 21, 2024.
Wen, Xiaobin, Lixin Tang, Ruqing Zhong, Lei Liu, Liang Chen, Hongfu Zhang. "Role of Mitophagy in Regulating Intestinal Oxidative Damage" Encyclopedia, https://encyclopedia.pub/entry/41461 (accessed December 21, 2024).
Wen, X., Tang, L., Zhong, R., Liu, L., Chen, L., & Zhang, H. (2023, February 21). Role of Mitophagy in Regulating Intestinal Oxidative Damage. In Encyclopedia. https://encyclopedia.pub/entry/41461
Wen, Xiaobin, et al. "Role of Mitophagy in Regulating Intestinal Oxidative Damage." Encyclopedia. Web. 21 February, 2023.
Role of Mitophagy in Regulating Intestinal Oxidative Damage
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This entry is adapted from the peer-reviewed paper 10.3390/antiox12020480

The mitochondrion is also a major site for maintaining redox homeostasis between reactive oxygen species (ROS) generation and scavenging. The quantity, quality, and functional integrity of mitochondria are crucial for regulating intracellular homeostasis and maintaining the normal physiological function of cells. The role of oxidative stress in human disease is well established, particularly in inflammatory bowel disease and gastrointestinal mucosal diseases. Oxidative stress could result from an imbalance between ROS and the antioxidative system. Mitochondria are both the main sites of production and the main target of ROS. It is a vicious cycle in which initial ROS-induced mitochondrial damage enhanced ROS production that, in turn, leads to further mitochondrial damage and eventually massive intestinal cell death. Oxidative damage can be significantly mitigated by mitophagy, which clears damaged mitochondria. 

ROS oxidative stress mitophagy PINK1-Parkin

1. Mitophagy Pathway

Not only do mitochondria produce ROS in large quantities, but they are also a primary target for ROS attacks [1][2]. Physiological ROS is important for cellular function and survival signaling, yet excess ROS-elicited oxidative stress leads to cell death [3][4]. There is a vicious cycle in which initial mitochondrial damage leads to ROS production, which creates further mitochondrial damage and eventually leads to massive intestinal cell death. To protect cells from oxidative damage, cells have developed an elaborate self-protective mechanism for selective degradation of the dysfunctional mitochondrion before it hurts the cell, called mitochondrial autophagy, or mitophagy [5]. Mitophagy is a term that was introduced by Lemasters in 2005 and designates the removal of dysfunctional mitochondria and their harmful byproducts and oxidative species to help maintain homeostasis [6][7]. Specifically, under the stimulation of starvation, hypoxia, energy deficiency, hormones, and exogenous infection, the bilayer membrane structures recognize and specifically wrap the mitochondria that are depolarized, dysfunctional, or produce high levels of ROS, and fuse with lysosomes to degrade these mitochondria, reducing the release of ROS and some pro-apoptotic factors from mitochondria. In mitophagy, the regulatory pathways can be classified as ubiquitin-dependent or ubiquitin-independent (receptor-dependent), respectively, based on whether the ubiquitin of the receptor recruit is required or not [8][9].

1.1. Ubiquitin-Dependent Mitophagy

PTEN-induced putative kinase 1 (PINK1)-cytosolic E3 ubiquitin ligase Parkin pathway represents one of the most studied ubiquitin-dependent mechanisms of mitophagy [7][10]. PINK1–Parkin has multiple roles in mitochondrial physiology, including mitochondrial dynamics, biogenesis, transport, and recruitment of autophagic machinery, to ensure the elimination of defective organelles [9]. PINK1 is an outer mitochondrial membrane (OMM) protein with Ser/Thr protein kinase activity [7]. Parkin (PARK2) is an E3 ubiquitin-protein ligase that mediates protein degradation and signal transduction in the cell [11]. In mammals, PINK1 and Parkin are expressed in many organs and tissues, such as the brain, skeletal muscles, heart, gut, and liver. In the inner mitochondrial membrane (IMM), PINK1 is continuously imported through translocase complexes between the outer and inner membranes, and is then degraded by various proteases, such as mitochondria-processing protease (MPP) and the inner membrane presenilin-related rhomboid-like protease (PARL) [10][12]. As a result, PINK1 is maintained at a low level in normal mitochondria, keeping its autophagy capacity at normal levels. When mitochondria are damaged or the membrane potential (ΔΨm) is depolarized, the inward transport and degradation of PINK1 will be inhibited, resulting in the accumulation of PINK1 in the OMM. This means that PINK1 likely acts as a mitochondrial damage sensor, activating Parkin to translocate from the cytoplasm to mitochondria [7]. In addition, the disruption of PINK1 phosphorylation blocks the Parkin’s translocation, while the deficiency of Parkin phosphorylation abolishes PINK1–Parkin-induced cell death [13]. As a consequence of its translocation, PINK1-dependent phosphorylation alters Parkin conformation, causing it to bind mitochondrial surfaces and trigger E3 ligase activity [9][14][15]. PINK1 also phosphorylates ubiquitin (Ub) and poly-Ub chains on dysfunctional mitochondria [9]. The inactivated Parkin binds to phospho-Ub and promotes its activation by PINK1. Parkin mediates the feedforward mechanism to generate poly-Ub chains, which is the substrate of PINK1, thus amplifying the autophagy signals [9][14][16]. Therefore, the significance of PINK1 in the mitochondria is needed in cell-protective characteristics for combating oxidative stress [17]. As a result of poly-Ub chains being phosphorylated by PINK1 and serving as an “eat me” signal for the autophagic machinery, the adaptor proteins recognize phosphorylated poly-Ub chains on mitochondrial proteins (p62, OPTN, NDP52, TAXBP1) and bind with the LC3 receptor to begin autophagosome formation [9].
In addition to mitophagy, the PINK1–Parkin pathway plays a vital role in mitochondrial movement as well [18][19]. Mitochondrial fission and fusion are affected at different levels by the PINK1–Parkin pathway [20]. Mitochondrial fusion is induced by the homo- or hetero-dimerization of the mitofusins (MFNs) 1 and 2, which tether the mitochondria together, pull the mitochondria that are in close proximity, and mediate fusion [21][22]. On the other hand, the mitochondrial fission process is orchestrated by the GTPase dynamin-related protein 1 (DRP1) [20]. DRP1 activity is indirectly triggered by PINK1 and promotes the fission of dysfunctional mitochondria, which enables their autophagic degradation [20][23]. In coordination with DRP1 activation, PINK1–Parkin-mediated phosphorylation and proteasomal degradation of MFN1 also contribute to mitochondrial fragmentation and the removal of dysfunctional organelles [24]. Additionally, MFN2 may function as a scaffold protein to facilitate Parkin translocation when mitochondrial damage occurs [9]. Specifically, MFN2 mediates the recruitment of Parkin to damaged mitochondria, and PINK1 phosphorylates MFN2 and promotes its ubiquitination by Parkin [10][24]. In this way, PINK1–Parkin activation causes rapid ubiquitination and degradation, preventing damaged mitochondria from fusing with healthy organelles [10][24]. There is evidence that healthy organelles and mitochondria contacts play a critical role in mitophagy, where PINK1–Parkin activation and deubiquitylation events occur. In addition to this, mitochondrial membrane potential dissipation stimulates PINK1-dependent phosphorylation of Miro, a Rho–GTPase of the OMM that anchors mitochondria to the cytoskeleton [9]. By ubiquitinating Miro, Parkin promotes its degradation while inhibiting mitochondrial transport. This causes mitochondria to dissociate from tubulin and separate from the mitochondrial network [9][18]. Therefore, blocking mitochondrial transport and enhancing fission could facilitate mitophagy, possibly by reducing mitochondria’s mobility and enabling them to be sequestered by autophagosomes. In addition, Parkin can also interact with Ambra1 to activate class III PI3K complexes (Vps34) around mitochondria to promote mitochondrial autophagy [25][26].
In addition to Parkin, a number of other ubiquitin E3 ligases are involved in the regulation of mitophagy, including Gp78, SMURF1, SIAH1, MUL1, and ARIH1 [9][10][27][28][29]. Their presence on the mitochondrial surface triggers the recruitment of autophagy adaptors, including optineurin (OPTN), nuclear dot protein 52 (NDP52), and p62, among others, by generating ubiquitin chains. In autophagy, autophagic components, like unc-51-like autophagy activating kinase 1 (ULK1), double FYVE-domain-containing protein 1 (DFCP1), and WD repeat domain, phosphoinositide interacting 1 (WIPI1), are recruited for the biogenesis of phagophores and expansion of autophagosome membranes [9][27][30].

1.2. Ubiquitin-Independent Mitophagy (Receptor-Dependent)

Apart from ubiquitin-dependent mitophagy, mitochondrial proteins serve as mitophagy receptors, mediating ubiquitin-independent mitophagy, also known as receptor-dependent mitophagy [9][29]. The OMM proteins BNIP3 (BCL2 interacting protein 3), NIX (NIP3-like protein X), and FUNDC1 (FUN14 domain-containing protein 1) are mitophagy receptors that fine-tune mitochondrial populations in response to various stimuli [9]. These mitophagy receptors directly or indirectly interact with the LC3 protein and lead to the selective degradation of mitochondria [31]. In addition, the activities of these mitophagy receptors are regulated by the phosphorylation status of their LIR [32]. During hypoxic conditions, BNIP3 and NIX, which belongs to the subfamily of BH3-only proteins, are induced and localized to the OMM through its carboxy-terminal transmembrane domain [31]. BNIP3 and NIX share the same LIR domains, and these LIR domains help BNIP3 and NIX bind to LC3 on autophagosomes. BNIP3 interferes with mitochondrial dynamics, promoting the fission of damaged organelles through the disassembly and release of OPA1, and recruitment of DRP1 to the mitochondrial surface [33][34]. In addition, BNIP3 increases mitophagy by suppressing the cleavage of PINK1. BNIP3 and its homolog NIX can not only promote apoptosis through the BH3 domains, but also induce mitophagy through the LIR motifs [35]. During reticulocyte development, NIX was shown to be required for mitochondrial clearance, while BNIP3 was identified to mediate mitophagy in cardiomyocytes and liver cells [33][34]. In addition to participating in ubiquitin-independent mitophagy, NIX also acts as a substrate of Parkin, recruiting NBR1 and ultimately triggering mitophagy [10]. FUNDC1 is located in the OMM and is associated with mitophagy under hypoxia or mitochondrial membrane potential dissipation [31]. FUNDC1 binds to LC3 via a conserved LIR motif and this interaction is enhanced under hypoxic conditions, facilitating mitochondrial engulfment by autophagosomes [20]. Phosphorylation of FUNDC1 and the consequent inhibition of FUNCD1-mediated mitophagy leads to excessive ROS accumulation [20][36]. Knockout of endogenous FUNDC1 significantly inhibited hypoxia-induced mitophagy [37]. It is attractive to hypothesize that NIX, BNIP3, and FUNDC1 act synergistically during hypoxia, with the results that FUNDC1 selectively targets mitochondria to autophagosomes formation via NIX- and BNIP3-mediated Beclin 1 activation [18]. Apart from the above, other mitophagy protein receptors of OMM include autophagy and Beclin 1 regulator 1 (AMBRA1), FKBP prolyl isomerase 8 (FKBP8), BCL2 like 13 (BCL2L13), and Prohibitins (PHB) [10][38].

2. Mitophagy and Oxidative Stress in Intestinal Disease

ROS regulates mitophagy by mediating the PINK1–Parkin pathway through its receptors or effector proteins. PINK1–Parkin pathway regulation of mitophagy also plays an important role in different oxidative damage diseases. The continuous differentiation and renewal of intestinal cells require a large amount of energy, which is accompanied by the production of ROS in the oxidative respiration chain of mitochondria [20][39]. Therefore, ROS is extremely active in intestinal epithelial cells, and its excessive accumulation can easily induce oxidative damage and lead to mitophagy, which is an important factor in the occurrence of various intestinal diseases.
Ulcerative colitis (UC) is a chronic inflammatory bowel disease with inflammation and ulceration of the colonic mucosa [40]. Oxidative stress and mitochondrial dysfunction are related to the pathogenesis of UC, and the incidence and severity of UC are correlated with the increase in ROS. Studies have found that high concentrations of oxidative molecules can be detected in plasma, serum, and even exhaled gas and saliva of UC patients, and the severity of UC is positively correlated with oxidative stress [41]. It has been confirmed that MnSOD and CAT expressions are decreased in UC, while MDA and GPX2 expressions are increased [42][43][44]. The antioxidant appearances were the same in the DSS-induced colitis mouse model, and the expression levels of ROS, IL-1β, and IL-18 in mitochondria decreased after treatment with the mitochondrial-targeted antioxidant MitQ [45]. Therefore, oxidative stress plays a critical role in UC pathogenesis and can be used as a therapeutic target and evaluation indicator. DSS-induced mitochondria in the rat model were in ridge collapse, expansion, and fragmentation states, and the membrane potential changes were reduced by 70% as compared with those in the normal mice [46]. Oxidative stress results in mitochondrial damage in UC patients, PINK1 and Parkin expressions are increased in UC, and mitophagy is activated as a protective mechanism [47]. Mitochondria can regulate the pro-inflammatory response of cells by activating molecular complexes of inflammasomes. ROS can cause NLRP3 to form a complex with apoptosis-associated speck-like protein that further enforces the precursor Caspase-1 to form the active NLRP3 inflammasome, which stimulates caspase-1 cleavage and releases activated IL-1β and IL-18 [48]. Mitochondria can also induce intestinal inflammation by signal transduction through pattern recognition receptors [49]. In conclusion, in ulcerative colitis, cells clear damaged mitochondria and overloaded ROS through mitophagy, thus protecting the colonic mucosa from damage. However, the exact route is still unclear, and further research is required in the future.
Crohn’s disease (CD) is referred to as regional enteritis due to the typical pattern of multifocal involvement with intervening normal tissue, “skip lesions”, which can involve any area of the gastrointestinal tract [50]. In patients with CD, oxidative stress and the accumulation of damaged intracellular macromolecules are important contributors to mucosal deterioration and increased intestinal permeability [51][52][53][54]. The ROS levels in CD patients are imbalanced with the antioxidant defenses. Moreover, the impaired and reduced Paneth cell is an important mechanism for the development of intestinal pathology in CD. Khaloian et al. reported that CD-like inflammation was negatively correlated with reduced Paneth cell function and LGR5-expression, and mitochondrial metabolic disorders can be induced by the absence of HSP60 in intestinal stem cells [55]. Jackson et al. also identified Paneth cells as highly susceptible to mitochondrial dysfunction and play a key role in ileitis pathogenesis, with translational implications for the subset of Crohn’s disease patients exhibiting Paneth cell defects [56]. Mitochondrial protein abundance in the ileum and colon of CD patients was significantly lower than that in the normal population, and CD patients show high mitochondrial activity of electrical signals in the ileum [57][58]. OPTN is a primary receptor required for the selective autophagy of damaged mitochondria [59]. Studies have found that OPTN is closely related to CD [60]. At present, there are few studies on CD and mitophagy. However, autophagy-related gene polymorphism is indeed associated with the pathogenesis of CD.
While the role of mitophagy in the development of IBD is now beginning to be understood, there is still a lot to be discovered. Additionally, some researchers have conducted many experiments using a model simulating intestinal oxidative damage. H2O2 is both an exogenous and endogenous pro-oxidative mediator that can lead to lipid peroxidation within the cell membranes and destroy the structure and function of the cell membrane, so it has been utilized in establishing an oxidative stress model in vitro [61][62][63][64][65]. A recent study reported that curcumin can effectively ameliorate H2O2-induced oxidative stress, intestinal epithelial barrier injury, and mitochondrial damage in IPEC-J2 cells in a PINK1–Parkin mitophagy-dependent way, and the authors also found depletion of Parkin abolished curcumin’s protective action on anti-oxidative stress [66]. Moreover, the same results were obtained with other drugs, such as sodium butyrate [67], selenium nanoparticles (SeNPs) [68], and resveratrol [69]. Consistent with in vitro data, dietary curcumin protected intestinal barrier function, improved redox status, alleviated mitochondrial damage, and triggered mitophagy in a well-established pig oxidative stress model by challenging with diquat [66][70][71]. Similarly, resveratrol can induce mitophagy in the intestine to alleviate the intestinal barrier dysfunction induced by oxidative stress [70].

References

  1. Li, N.; Stojanovski, S.; Maechler, P. Mitochondrial hormesis in pancreatic β cells: Does uncoupling protein 2 play a role? Oxid. Med. Cell Longev. 2012, 2012, 740849.
  2. Yao, N.; Li, Y.J.; Lei, Y.H.; Hu, N.; Chen, W.M.; Yao, Z.; Yu, M.; Liu, J.S.; Ye, W.C.; Zhang, D.M. A piperazidine derivative of 23-hydroxy betulinic acid induces a mitochondria-derived ROS burst to trigger apoptotic cell death in hepatocellular carcinoma cells. J. Exp. Clin. Cancer Res. 2016, 35, 192.
  3. Nelson, K.K.; Melendez, J.A. Mitochondrial redox control of matrix metalloproteinases. Free Radic. Biol. Med. 2004, 37, 768–784.
  4. Chien, C.-C.; Wu, M.-S.; Shen, S.-C.; Ko, C.-H.; Chen, C.-H.; Yang, L.-L.; Chen, Y.-C. Activation of JNK contributes to evodiamine-induced apoptosis and G2/M arrest in human colorectal carcinoma cells: A structure-activity study of evodiamine. PLoS ONE 2014, 9, e99729.
  5. Saita, S.; Shirane, M.; Nakayama, K.I. Selective escape of proteins from the mitochondria during mitophagy. Nat. Commun. 2013, 4, 1410.
  6. Lemasters, J.J. Selective mitochondrial autophagy, or mitophagy, as a targeted defense against oxidative stress, mitochondrial dysfunction, and aging. Rejuvenation Res. 2005, 8, 3–5.
  7. Shefa, U.; Jeong, N.Y.; Song, I.O.; Chung, H.J.; Kim, D.; Jung, J.; Huh, Y. Mitophagy links oxidative stress conditions and neurodegenerative diseases. Neural Regen. Res. 2019, 14, 749–756.
  8. Vernucci, E.; Tomino, C.; Molinari, F.; Limongi, D.; Aventaggiato, M.; Sansone, L.; Tafani, M.; Russo, M.A. Mitophagy and oxidative stress in cancer and aging: Focus on sirtuins and nanomaterials. Oxid. Med. Cell Longev. 2019, 2019, 6387357.
  9. Palikaras, K.; Lionaki, E.; Tavernarakis, N. Mechanisms of mitophagy in cellular homeostasis, physiology and pathology. Nat. Cell Biol. 2018, 20, 1013–1022.
  10. De Gaetano, A.; Gibellini, L.; Zanini, G.; Nasi, M.; Cossarizza, A.; Pinti, M. Mitophagy and oxidative stress: The role of aging. Antioxidants 2021, 10, 794.
  11. Lee, D.H.; Park, M.H.; Hwang, C.J.; Kim, Y.; Hwang, D.Y.; Han, S.B.; Hong, J.T. Parkin deficiency prevents chronic ethanol-induced hepatic lipid accumulation through β-catenin accumulation. Cell Commun. Signal. 2019, 17, 104.
  12. Meissner, C.; Lorenz, H.; Hehn, B.; Lemberg, M.K. Intramembrane protease PARL defines a negative regulator of PINK1- and PARK2/Parkin-dependent mitophagy. Autophagy 2015, 11, 1484–1498.
  13. Zhuang, N.; Li, L.; Chen, S.; Wang, T. PINK1-dependent phosphorylation of PINK1 and Parkin is essential for mitochondrial quality control. Cell Death Dis. 2016, 7, e2501.
  14. Harper, J.W.; Ordureau, A.; Heo, J.-M. Building and decoding ubiquitin chains for mitophagy. Nat. Rev. Mol. Cell Biol. 2018, 19, 93–108.
  15. Aguirre, J.D.; Dunkerley, K.M.; Mercier, P.; Shaw, G.S. Structure of phosphorylated UBL domain and insights into PINK1-orchestrated parkin activation. Proc. Natl. Acad. Sci. USA 2017, 114, 298–303.
  16. Ordureau, A.; Sarraf, S.A.; Duda, D.M.; Heo, J.-M.; Jedrychowski, M.P.; Sviderskiy, V.O.; Olszewski, J.L.; Koerber, J.T.; Xie, T.; Beausoleil, S.A.; et al. Quantitative proteomics reveal a feedforward mechanism for mitochondrial PARKIN translocation and ubiquitin chain synthesis. Mol. Cell 2014, 56, 360–375.
  17. Eiyama, A.; Okamoto, K. PINK1/Parkin-mediated mitophagy in mammalian cells. Curr. Opin. Cell Biol. 2015, 33, 95–101.
  18. Ashrafi, G.; Schwarz, T.L. The pathways of mitophagy for quality control and clearance of mitochondria. Cell Death Differ. 2013, 20, 31–42.
  19. Luciani, A.; Schumann, A.; Berquez, M.; Chen, Z.; Nieri, D.; Failli, M.; Debaix, H.; Festa, B.P.; Tokonami, N.; Raimondi, A.; et al. Impaired mitophagy links mitochondrial disease to epithelial stress in methylmalonyl-CoA mutase deficiency. Nat. Commun. 2020, 11, 970.
  20. Scheffer, D.d.L.; Garcia, A.A.; Lee, L.; Mochly-Rosen, D.; Ferreira, J.C.B. Mitochondrial fusion, fission, and mitophagy in cardiac diseases: Challenges and therapeutic opportunities. Antioxid. Redox. Signal. 2022, 36, 844–863.
  21. Wai, T.; Langer, T. Mitochondrial dynamics and metabolic regulation. Trends Endocrinol. Metab. 2016, 27, 105–117.
  22. Zhang, Y.; Liu, X.; Bai, J.; Tian, X.; Zhao, X.; Liu, W.; Duan, X.; Shang, W.; Fan, H.-Y.; Tong, C. Mitoguardin regulates mitochondrial fusion through MitoPLD and is required for neuronal homeostasis. Mol. Cell 2016, 61, 111–124.
  23. Pryde, K.R.; Smith, H.L.; Chau, K.-Y.; Schapira, A.H.V. PINK1 disables the anti-fission machinery to segregate damaged mitochondria for mitophagy. J. Cell Biol. 2016, 213, 163–171.
  24. Tanaka, A.; Cleland, M.M.; Xu, S.; Narendra, D.P.; Suen, D.-F.; Karbowski, M.; Youle, R.J. Proteasome and p97 mediate mitophagy and degradation of mitofusins induced by Parkin. J. Cell Biol. 2010, 191, 1367–1380.
  25. Strappazzon, F.; Nazio, F.; Corrado, M.; Cianfanelli, V.; Romagnoli, A.; Fimia, G.M.; Campello, S.; Nardacci, R.; Piacentini, M.; Campanella, M.; et al. AMBRA1 is able to induce mitophagy via LC3 binding, regardless of PARKIN and p62/SQSTM1. Cell Death Differ. 2015, 22, 419–432.
  26. Kagan, V.E.; Jiang, J.; Huang, Z.; Tyurina, Y.Y.; Desbourdes, C.; Cottet-Rousselle, C.; Dar, H.H.; Verma, M.; Tyurin, V.A.; Kapralov, A.A.; et al. NDPK-D (NM23-H4)-mediated externalization of cardiolipin enables elimination of depolarized mitochondria by mitophagy. Cell Death Differ. 2016, 23, 1140–1151.
  27. Li, A.; Gao, M.; Liu, B.; Qin, Y.; Chen, L.; Liu, H.; Wu, H.; Gong, G. Mitochondrial autophagy: Molecular mechanisms and implications for cardiovascular disease. Cell Death Dis. 2022, 13, 444.
  28. Montava-Garriga, L.; Ganley, I.G. Outstanding questions in mitophagy: What we do and do not know. J. Mol. Biol. 2020, 432, 206–230.
  29. Praharaj, P.P.; Naik, P.P.; Panigrahi, D.P.; Bhol, C.S.; Mahapatra, K.K.; Patra, S.; Sethi, G.; Bhutia, S.K. Intricate role of mitochondrial lipid in mitophagy and mitochondrial apoptosis: Its implication in cancer therapeutics. Cell Mol. Life Sci. 2019, 76, 1641–1652.
  30. Lazarou, M.; Sliter, D.A.; Kane, L.A.; Sarraf, S.A.; Wang, C.; Burman, J.L.; Sideris, D.P.; Fogel, A.I.; Youle, R.J. The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy. Nature 2015, 524, 309–314.
  31. Panigrahi, D.P.; Praharaj, P.P.; Bhol, C.S.; Mahapatra, K.K.; Patra, S.; Behera, B.P.; Mishra, S.R.; Bhutia, S.K. The emerging, multifaceted role of mitophagy in cancer and cancer therapeutics. Semin Cancer Biol. 2020, 66, 45–58.
  32. Birgisdottir, Å.B.; Lamark, T.; Johansen, T. The LIR motif—Crucial for selective autophagy. J. Cell Sci 2013, 126, 3237–3247.
  33. Liu, K.; Zhao, Q.; Sun, H.; Liu, L.; Wang, C.; Li, Z.; Xu, Y.; Wang, L.; Zhang, L.; Zhang, H.; et al. BNIP3 (BCL2 interacting protein 3) regulates pluripotency by modulating mitochondrial homeostasis via mitophagy. Cell Death Dis. 2022, 13, 334.
  34. Quinsay, M.N.; Thomas, R.L.; Lee, Y.; Gustafsson, A.B. Bnip3-mediated mitochondrial autophagy is independent of the mitochondrial permeability transition pore. Autophagy 2010, 6, 855–862.
  35. Hamacher-Brady, A.; Brady, N.R. Mitophagy programs: Mechanisms and physiological implications of mitochondrial targeting by autophagy. Cell Mol. Life Sci. 2016, 73, 775–795.
  36. Zhou, H.; Zhu, P.; Wang, J.; Zhu, H.; Ren, J.; Chen, Y. Pathogenesis of cardiac ischemia reperfusion injury is associated with CK2α-disturbed mitochondrial homeostasis via suppression of FUNDC1-related mitophagy. Cell Death Differ. 2018, 25, 1080–1093.
  37. Wang, J.; Zhu, P.; Li, R.; Ren, J.; Zhou, H. Fundc1-dependent mitophagy is obligatory to ischemic preconditioning-conferred renoprotection in ischemic AKI via suppression of Drp1-mediated mitochondrial fission. Redox. Biol. 2020, 30, 101415.
  38. Wei, Y.; Chiang, W.C.; Sumpter, R., Jr.; Mishra, P.; Levine, B. Prohibitin 2 is an inner mitochondrial membrane mitophagy receptor. Cell 2017, 168, 224–238.e10.
  39. Wang, M.; Hu, R.; Wang, Y.; Liu, L.; You, H.; Zhang, J.; Wu, X.; Pei, T.; Wang, F.; Lu, L.; et al. Atractylenolide III attenuates muscle wasting in chronic kidney disease via the oxidative stress-mediated PI3K/AKT/mTOR pathway. Oxid. Med. Cell Longev. 2019, 2019, 1875471.
  40. Wang, Q.; Hou, Y.; Yi, D.; Wang, L.; Ding, B.; Chen, X.; Long, M.; Liu, Y.; Wu, G. Protective effects of N-acetylcysteine on acetic acid-induced colitis in a porcine model. BMC Gastroenterol. 2013, 13, 133.
  41. Arab, H.H.; Al-Shorbagy, M.Y.; Abdallah, D.M.; Nassar, N.N. Telmisartan attenuates colon inflammation, oxidative perturbations and apoptosis in a rat model of experimental inflammatory bowel disease. PLoS ONE 2014, 9, e97193.
  42. Mangerich, A.; Dedon, P.C.; Fox, J.G.; Tannenbaum, S.R.; Wogan, G.N. Chemistry meets biology in colitis-associated carcinogenesis. Free Radic. Res. 2013, 47, 958–986.
  43. Bouzid, D.; Gargouri, B.; Mansour, R.B.; Amouri, A.; Tahri, N.; Lassoued, S.; Masmoudi, H. Oxidative stress markers in intestinal mucosa of Tunisian inflammatory bowel disease patients. Saudi J. Gastroenterol. 2013, 19, 131–135.
  44. Dudzińska, E.; Gryzinska, M.; Ognik, K.; Gil-Kulik, P.; Kocki, J. Oxidative stress and effect of treatment on the oxidation product decomposition processes in IBD. Oxid. Med. Cell Longev. 2018, 2018, 7918261.
  45. Dashdorj, A.; Jyothi, K.R.; Lim, S.; Jo, A.; Nguyen, M.N.; Ha, J.; Yoon, K.S.; Kim, H.J.; Park, J.H.; Murphy, M.P.; et al. Mitochondria-targeted antioxidant MitoQ ameliorates experimental mouse colitis by suppressing NLRP3 inflammasome-mediated inflammatory cytokines. BMC Med. 2013, 11, 178.
  46. Wang, D.; Zhang, Y.; Yang, S.; Zhao, D.; Wang, M. A polysaccharide from cultured mycelium of Hericium erinaceus relieves ulcerative colitis by counteracting oxidative stress and improving mitochondrial function. Int. J. Biol. Macromol. 2019, 125, 572–579.
  47. Mai, C.T.; Wu, M.M.; Wang, C.L.; Su, Z.R.; Cheng, Y.Y.; Zhang, X.J. Palmatine attenuated dextran sulfate sodium (DSS)-induced colitis via promoting mitophagy-mediated NLRP3 inflammasome inactivation. Mol. Immunol. 2019, 105, 76–85.
  48. Lopez-Armada, M.J.; Riveiro-Naveira, R.R.; Vaamonde-Garcia, C.; Valcarcel-Ares, M.N. Mitochondrial dysfunction and the inflammatory response. Mitochondrion 2013, 13, 106–118.
  49. West, A.P.; Shadel, G.S.; Ghosh, S. Mitochondria in innate immune responses. Nat. Rev. Immunol. 2011, 11, 389–402.
  50. McGary, C.T.; Lowe, M.C. Educational case: Idiopathic inflammatory bowel disease. Acad. Pathol. 2020, 7, 2374289520937433.
  51. Veres-Székely, A.; Bernáth, M.; Pap, D.; Rokonay, R.; Szebeni, B.; Takács, I.M.; Lippai, R.; Cseh, Á.; Szabó, A.J.; Vannay, Á. PARK7 diminishes oxidative stress-induced mucosal damage in celiac disease. Oxid. Med. Cell Longev. 2020, 2020, 4787202.
  52. Szaflarska-Poplawska, A.; Siomek, A.; Czerwionka-Szaflarska, M.; Gackowski, D.; Rózalski, R.; Guz, J.; Szpila, A.; Zarakowska, E.; Olinski, R. Oxidatively damaged DNA/oxidative stress in children with celiac disease. Cancer Epidemiol. Biomark. Prev. 2010, 19, 1960–1965.
  53. Alzoghaibi, M.A. Concepts of oxidative stress and antioxidant defense in Crohn’s disease. World J. Gastroenterol. 2013, 19, 6540–6547.
  54. Liu, J.; Zhang, L.; Wang, Z.; Chen, S.; Feng, S.; He, Y.; Zhang, S. Network pharmacology-based strategy to identify the pharmacological mechanisms of pulsatilla decoction against Crohn’s disease. Front. Pharmacol. 2022, 13, 844685.
  55. Khaloian, S.; Rath, E.; Hammoudi, N.; Gleisinger, E.; Blutke, A.; Giesbertz, P.; Berger, E.; Metwaly, A.; Waldschmitt, N.; Allez, M.; et al. Mitochondrial impairment drives intestinal stem cell transition into dysfunctional Paneth cells predicting Crohn’s disease recurrence. Gut 2020, 69, 1939–1951.
  56. Jackson, D.N.; Panopoulos, M.; Neumann, W.L.; Turner, K.; Cantarel, B.L.; Thompson-Snipes, L.; Dassopoulos, T.; Feagins, L.A.; Souza, R.F.; Mills, J.C.; et al. Mitochondrial dysfunction during loss of prohibitin 1 triggers Paneth cell defects and ileitis. Gut 2020, 69, 1928–1938.
  57. Pierre, N.; Salée, C.; Massot, C.; Blétard, N.; Mazzucchelli, G.; Smargiasso, N.; Morsa, D.; Baiwir, D.; De Pauw, E.; Reenaers, C.; et al. Proteomics Highlights Common and Distinct Pathophysiological Processes Associated with Ileal and Colonic Ulcers in Crohn’s Disease. J. Crohns. Colitis. 2020, 14, 205–215.
  58. Kugathasan, S.; Denson, L.A.; Walters, T.D.; Kim, M.O.; Marigorta, U.M.; Schirmer, M.; Mondal, K.; Liu, C.; Griffiths, A.; Noe, J.D.; et al. Prediction of complicated disease course for children newly diagnosed with Crohn’s disease: A multicentre inception cohort study. Lancet 2017, 389, 1710–1718.
  59. Dominguez, J.; Yu, J.T.; Tan, Y.J.; Ng, A.; De Guzman, M.F.; Natividad, B.; Daroy, M.L.; Cano, J.; Yu, J.; Lian, M.M.; et al. Novel optineurin frameshift insertion in a family with frontotemporal dementia and parkinsonism without amyotrophic lateral sclerosis. Front. Neurol. 2021, 12, 645913.
  60. Weil, R.; Laplantine, E.; Curic, S.; Génin, P. Role of optineurin in the mitochondrial dysfunction: Potential implications in neurodegenerative diseases and cancer. Front. Immunol. 2018, 9, 1243.
  61. Cao, S.; Xiao, H.; Li, X.; Zhu, J.; Gao, J.; Wang, L.; Hu, C. AMPK-PINK1/Parkin mediated mitophagy is necessary for alleviating oxidative stress-induced intestinal epithelial barrier damage and mitochondrial energy metabolism dysfunction in IPEC-J2. Antioxidants 2021, 10, 2010.
  62. Zou, Y.; Wang, J.; Peng, J.; Wei, H. Oregano essential oil induces SOD1 and GSH expression through Nrf2 activation and alleviates hydrogen peroxide-induced oxidative damage in IPEC-J2 Cells. Oxid. Med. Cell Longev. 2016, 2016, 5987183.
  63. Yin, J.; Wu, M.; Li, Y.; Ren, W.; Xiao, H.; Chen, S.; Li, C.; Tan, B.; Ni, H.; Xiong, X.; et al. Toxicity assessment of hydrogen peroxide on Toll-like receptor system, apoptosis, and mitochondrial respiration in piglets and IPEC-J2 cells. Oncotarget 2017, 8, 3124–3131.
  64. Wen, Z.S.; Ma, L.; Xiang, X.W.; Tang, Z.; Guan, R.F.; Qu, Y.L. Protective effect of low molecular-weight seleno-aminopolysaccharides against H2O2-induecd oxidative stress in intestinal epithelial cells. Int. J. Biol. Macromol. 2018, 112, 745–753.
  65. Liang, D.; Zhuo, Y.; Guo, Z.; He, L.; Wang, X.; He, Y.; Li, L.; Dai, H. SIRT1/PGC-1 pathway activation triggers autophagy/mitophagy and attenuates oxidative damage in intestinal epithelial cells. Biochimie 2020, 170, 10–20.
  66. Cao, S.; Wang, C.; Yan, J.; Li, X.; Wen, J.; Hu, C. Curcumin ameliorates oxidative stress-induced intestinal barrier injury and mitochondrial damage by promoting Parkin dependent mitophagy through AMPK-TFEB signal pathway. Free Radic. Biol. Med. 2020, 147, 8–22.
  67. Li, X.; Wang, C.; Zhu, J.; Lin, Q.; Yu, M.; Wen, J.; Feng, J.; Hu, C. Sodium butyrate ameliorates oxidative stress-induced intestinal epithelium barrier injury and mitochondrial damage through AMPK-Mitophagy pathway. Oxid. Med. Cell Longev. 2022, 2022, 3745135.
  68. Yan, S.; Qiao, L.; Dou, X.; Song, X.; Chen, Y.; Zhang, B.; Xu, C. Biogenic selenium nanoparticles by Lactobacillus casei ATCC 393 alleviate the intestinal permeability, mitochondrial dysfunction and mitophagy induced by oxidative stress. Food Funct. 2021, 12, 7068–7080.
  69. Chen, Y.; Zhang, H.; Ji, S.; Jia, P.; Chen, Y.; Li, Y.; Wang, T. Resveratrol and its derivative pterostilbene attenuate oxidative stress-induced intestinal injury by improving mitochondrial redox homeostasis and function via SIRT1 signaling. Free Radic. Biol. Med. 2021, 177, 1–14.
  70. Cao, S.; Shen, Z.; Wang, C.; Zhang, Q.; Hong, Q.; He, Y.; Hu, C. Resveratrol improves intestinal barrier function, alleviates mitochondrial dysfunction and induces mitophagy in diquat challenged piglets. Food Funct. 2019, 10, 344–354.
  71. Cao, S.; Wu, H.; Wang, C.; Zhang, Q.; Jiao, L.; Lin, F.; Hu, C.H. Diquat-induced oxidative stress increases intestinal permeability, impairs mitochondrial function, and triggers mitophagy in piglets. J. Anim. Sci. 2018, 96, 1795–1805.
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Subjects: Cell Biology
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Xiaobin Wen
,
Lixin Tang
,
Ruqing Zhong
,
Lei Liu
,
Liang Chen
,
Hongfu Zhang
View Times: 302
Revisions: 2 times (View History)
Update Date: 22 Feb 2023
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