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
Chao Sun
 -- 2157 2024-02-01 02:34:08 |
2 layout
Jessie Wu
 -3 word(s) 2154 2024-02-01 03:03:27 | |
3 layout
Jessie Wu
 Meta information modification 2154 2024-02-01 03:04:13 |

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.
Hu, C.; Shi, Z.; Liu, X.; Sun, C. Mitochondrial Transplantation for Mitochondria-Deficient Diseases. Encyclopedia. Available online: https://encyclopedia.pub/entry/54618 (accessed on 18 May 2024).
Hu C, Shi Z, Liu X, Sun C. Mitochondrial Transplantation for Mitochondria-Deficient Diseases. Encyclopedia. Available at: https://encyclopedia.pub/entry/54618. Accessed May 18, 2024.
Hu, Cuilan, Zheng Shi, Xiongxiong Liu, Chao Sun. "Mitochondrial Transplantation for Mitochondria-Deficient Diseases" Encyclopedia, https://encyclopedia.pub/entry/54618 (accessed May 18, 2024).
Hu, C., Shi, Z., Liu, X., & Sun, C. (2024, February 01). Mitochondrial Transplantation for Mitochondria-Deficient Diseases. In Encyclopedia. https://encyclopedia.pub/entry/54618
Hu, Cuilan, et al. "Mitochondrial Transplantation for Mitochondria-Deficient Diseases." Encyclopedia. Web. 01 February, 2024.
Mitochondrial Transplantation for Mitochondria-Deficient Diseases
Edit
This entry is adapted from the peer-reviewed paper 10.3390/ijms25021175

Mitochondria are double-membrane organelles that are involved in energy production, apoptosis, and signaling in eukaryotic cells. Several studies conducted over the past decades have correlated mitochondrial dysfunction with various diseases, including cerebral ischemia, myocardial ischemia-reperfusion, and cancer. Mitochondrial transplantation entails importing intact mitochondria from healthy tissues into diseased tissues with damaged mitochondria to rescue the injured cells. 

mitochondrial transplantation mitochondrial defective diseases cerebral ischemia myocardial ischemia-reperfusion cancer

1. Mitochondrial Transplantation Protects against Neuronal Damage Caused by Cerebral Ischemia

Cerebral ischemia or stroke is a condition caused by insufficient blood supply to the brain, resulting in hypoxia and damage to brain tissue. Severe cerebral ischemia or stroke can lead to neuronal damage and transient ischemic attacks [1]. Glutamate is a neurotransmitter in the central nervous system that mediates rapid excitatory synaptic responses upon binding to N-methyl-D-aspartate (NMDA)-type receptors on neuronal membranes [2]. High concentrations of glutamate have been detected in the cerebral cortex, hippocampus, and amygdala during cerebral ischemia and can cause severe neurotoxicity. NMDA receptor is a ligand-gated ion channel that is highly permeable to calcium ions. Glutamate binding effectively opens the Ca2+ channel [3], leading to an increase in intraneuronal Ca2+ concentrations [4]. The Ca2+ overload triggers the opening of the mitochondrial permeability transition pore (MPTP) [5], which prevents oxidative phosphorylation and ATP production, leading to mitochondrial membrane depolarization, ATP hydrolysis [6], and the release of NAD+ and Ca2+. The ensuing mitochondrial swelling and rupture releases ROS, cytochrome c, and other apoptosis-inducing factors [7][8]. The excessive amount of ROS released into the cytoplasm can also trigger ROS-induced ROS release (RIRR) in the neighboring mitochondria, leading to a vicious cycle of MPTP opening and continuous increase in ROS levels that ultimately leads to mitochondrial damage and cell death [9]. Transplantation of functionally normal mitochondria into injured neurons can reduce ROS production and restore ATP production, thus providing the cells with sufficient energy to activate mitochondria-targeted autophagy and enable repair [10]. Pourmohammadi-Bejarpasi et al. replicated an adult rat model of cerebral ischemia using nylon threads to block cerebral arteries and injected hucMSC-derived normal mitochondria directly into the brain using an ICV device. Examination of the brain tissue showed that the injected mitochondria were internalized into the neurons and astrocytes at the ischemic site, which was accompanied by a reduction in coagulative necrosis and restoration of normal cellular structure in the brain. In addition, the infarcted area, blood creatine phosphokinase levels, number of apoptotic cells and astrocytes, and microglial activation showed a significant decrease, resulting in improved motor function and coordination [11][12]. Existing studies have shown that Miro1 appears to be a key participant in mitochondrial transfer. In an epithelial cell injury model, Miro1 has the ability to regulate the intercellular movement of mitochondria from MSCs to epithelial cells (ECs). The overexpression of Miro1 enhances mitochondrial transfer, effectively reversing mitochondrial dysfunction in ECs and rescuing them [13]. Conversely, the knockdown of Miro1 leads to a loss of therapeutic effect. Tseng et al. conducted in vitro found that the transfer of mitochondria to oxidatively damaged neurons can improve neuronal preservation after an ischemic stroke and enhances neuronal metabolism. The research results revealed a decrease in neuronal viability and the presence of significant mitochondrial dysfunction following oxidative damage in vitro. However, co-cultivation with MCSs can restore mitochondrial function and significantly improve neuronal metabolic activity, including mitochondrial respiration and ATP production. Ischemia damages neuronal mitochondria and triggers an inflammatory response, resulting in an increased production of Miro1. This, in turn, promotes mitochondrial movement and the transfer of healthy mitochondria from MCSs to neurons, potentially safeguarding neurons from apoptosis [14]. These findings suggest that mitochondrial transplantation can effectively protect against acute cerebral ischemia.
Studies show that mitochondria can be transferred from astrocytes to neurons via CD38 and cyclic ADP-ribose (cADPR) signaling. SiRNA-mediated CD38 knockdown significantly reduced the number of mitochondria released from astrocytes as well as the number transferred into neuronal cells, which mitigated the protective effect against cerebral ischemia [15]. In addition, Li et al. demonstrated the protective effects of mitochondrial transfer and internalization against severe spinal cord injury [16]. Transcellular transfer of mitochondria opens up new avenues for treating diseases of the central nervous system as well as the peripheral nervous system [17]. Several studies have shown that mitochondrial transplantation protects against neuronal damage caused by cerebral ischemia and promotes the repair of injured cardiomyocytes [18] and lung epithelial cells [19].

2. Mitochondrial Transplantation for Myocardial Ischemia-Reperfusion Injury

The heart is an oxygen-demanding organ that requires a continuous supply of energy. Unsurprisingly, mitochondria account for approximately 30% of the cardiomyocyte volume, and the functional status of these mitochondria directly influences the fate of cardiomyocytes. During ischemia, reduced blood flow to the heart limits the delivery of oxygen and nutrients, leading to mitochondrial dysfunction and impaired ATP production. This energy deficit impairs cardiac muscle contraction and triggers a series of events that culminate in myocardial ischemia-reperfusion injury (IRI) [20]. Ischemic injury, in turn, disrupts the mitochondrial inner membrane and expands the mitochondrial matrix. Therefore, the replacement of injured mitochondria with intact functional mitochondria isolated from healthy cells or tissues is a promising therapeutic strategy against myocardial IRI [13]. The transplanted mitochondria can alleviate myocardial injury by restoring lipid and glucose metabolic pathways and generating sufficient energy for cardiac functions [21].
Sun et al. constructed PEP-TPP mitochondrial complexes through the ischemic sensitivity of PEP and the mitochondrial targeting ability of TPP+. These complexes were able to enter ischemia-damaged cardiomyocytes through direct internalization or via endothelial cells and enhanced the respiratory capacity and mechanical contractility of cardiomyocytes, decreased the levels of pro-inflammatory cytokines such as IL-2, and reduced cardiomyocyte apoptosis after transplantation. In a mouse model of infrared radiation injury, 7.5–10 × 104 intravenously injected PEP-TPP mitochondrial complexes promoted intraventricular mitochondrial engraftment in the ischemic myocardium, which significantly reduced the myocardial infarct area and provided long-term (2–4 weeks) protection against cardiomyocyte reperfusion injury [22]. The therapeutic effects of mitochondrial transplantation have also been demonstrated in rabbit and porcine models of cardiac IRI. McCully et al. isolated fresh, intact, viable, and respiring mitochondria from non-ischemic hearts. During the early reperfusion period, they injected these mitochondria into the ischemic zone to limit the damage caused by decreased mitochondrial function during ischemia. The study found that exogenous ATP and ADP were unable to protect the heart, while mitochondrial transplantation significantly reduced myocardial necrosis and cardiomyocyte apoptosis, markedly decreased infarct size (IS), caspase-3-like activity, TUNEL, as well as the release of creatine kinase isoenzymes (CK-MB) and cardiac troponin I (cTnI), alleviating myocardial injury and significantly enhancing regional and overall myocardial function recovery after ischemia [23]. Furthermore, autologous mitochondrial transplantation has unique therapeutic potential for improving ischemia-reperfusion injury and enhancing myocardial function. Isolation and preparation of autologous mitochondria from the patient’s body can prevent inflammation and rejection reactions. Masuzawa et al. observed that autologous mitochondrial transplantation led to the internalization of mitochondria by cardiomyocytes, followed by enhanced ATP production and enrichment in the generation of differentially expressed proteins associated with mitochondrial pathways and proteins responsible for the production of precursor metabolites related to energy and cellular respiration. Ultimately, this improved myocardial injury and enhances regional function [24].
Furthermore, the transplanted mitochondria in the ischemic regions of the heart exhibit intra- and extracellular functionality [25]. In one study, clusters of transplanted mitochondria were detected around the endogenous damaged mitochondria and in the vicinity of the nuclei of cardiomyocytes one hour after injection, and the damaged cells were protected by increasing oxygen consumption and ATP synthesis [24].
Apart from enhancing the energy supply to the injured myocardium, mitochondrial transplantation also initiates angiogenic, immunomodulatory, anti-apoptotic, anti-oxidant, and anti-inflammatory effects. In addition, the transplanted mitochondria can increase the circulating levels of epidermal growth factor (EGF), growth-regulated oncogenes (GRO), interleukin 6 (IL-6), monocyte chemotaxis protein 3 (MCP-3), and nuclear factor erythroid2-related factor 2 (Nrf2), which are related to the recovery of myocardial function [26][27]. During myocardial ischemia/reperfusion, EGF maintains the integrity of the myocardial endothelium by stimulating cardiomyocyte growth, proliferation, and migration [28][29]. After myocardial infarction, GRO and IL-6 promote vascularization and prevent apoptosis in the infarcted area. Along with MPC-3, these cytokines can rapidly improve cardiac remodeling after myocardial infarction through non-cardiomyocyte regenerative pathways [30]. Nrf2 activation also attenuates myocardial infarct size and preserves cardiac function through coordinated upregulation of anti-oxidant, anti-inflammatory, and autophagic mechanisms [17]. In addition, the internalized normal mtDNA can replace damaged mtDNA and exert a cardio-protective effect at the genetic level [5][31].
Mitochondrial transplantation was clinically tested for the first time in 2016 in pediatric patients with myocardial IRI. Five patients experiencing extracorporeal membrane pulmonary oxygenation (ECMO) were treated with local injections of autologous normal mitochondria isolated from the rectus abdominis muscle [32]. The systolic function improved significantly in all five patients, including four children with ischemia-induced coronary artery obstruction and one child with subepicardial ischemia-induced left ventricular hypertrophy [18]. Taken together, mitochondrial transplantation can improve myocardial function in animal models and humans and is a promising therapeutic strategy against cardiac IRI. It can be used alone or in combination with other clinical interventions, or as an adjunct to other clinical interventions. Given the availability of simple and rapid techniques for high-purity mitochondrial isolation, this approach can be applied on a large scale.

3. Mitochondrial Transplantation for Tumor Therapy

Mitochondrial dysfunction triggers the release of various death factors such as ROS, Ca2+, and cytochrome c, resulting in oxidative stress [33] and cellular damage [34]. Aberrant mitochondrial function and ROS overproduction in the tumor cells trigger mutations in mtDNA and nuclear DNA, leading to impaired oxidative phosphorylation that exacerbates ROS production and creates a vicious cycle [35]. The altered redox balance activates signaling pathways involved in cell survival, proliferation, and angiogenesis, further promoting tumor growth [36]. Cancer cells undergo metabolic reprogramming with an increase in glycolysis rates, a phenomenon known as the Warburg effect [37][38][39]. This transformation not only allows cancer cells to meet the energy needs for rapid proliferation [40] but also underlies radio-resistance and chemoresistance in tumors. Therefore, inhibiting glycolysis in tumor cells can sensitize them to radiation or chemotherapeutic drugs and overcome treatment resistance [41][42]. Mitochondrial transplantation in tumor cells can reduce aerobic glycolysis, block cell cycle progression by downregulating cycle-related proteins, and activate the intrinsic apoptosis pathway by upregulating pro-apoptotic proteins, eventually inhibiting cell proliferation [43]. Sun et al. found that endocytosis-mediated mitochondrial transplantation from normal human astrocytes to glioma cells rescued aerobic respiration, attenuated the Warburg effect, and improved radiosensitivity of gliomas. Furthermore, endocytosis of mitochondria into the glioma cells was mediated by nicotinamide adenine dinucleotide (NAD+)-CD38-cADPR-Ca2+ signaling [44]. CD38 is a single-chain type I transmembrane glycoprotein that catalyzes the generation of cADPR from NAD+ and transports cADPR into the cell in the form of a homodimer [45]. cADPR acts as a second messenger in the intracellular signaling cascade that mediates the release of intracytoplasmic Ca2+ and regulates changes in the cytoskeleton, endocytosis, or exocytosis, which may be responsible for transcellular mitochondrial transfer [46][47].
Elliott et al. co-cultured the mitochondria isolated from normal breast epithelial cells (MCF-12A) with breast cancer cell lines (MCF-7, MDA-MB-231, and NCI/ADR-Res). The introduction of normal mitochondria into the breast cancer cells inhibited proliferation and enhanced their sensitivity to doxorubicin, abraxane, and carboplatin [48]. Recent studies have shown that mitochondrial transplantation can also inhibit the proliferation of melanoma cells and induce apoptosis. Chang et al. isolated normal and A8344G-mutated mitochondria from homeoplasmic 143B osteosarcoma cells and delivered them to MCF-7 breast cancer cells through passive uptake or Pep-1. Mitochondrial transplantation induced apoptosis in the recipient cells by increasing nuclear translocation of apoptosis-inducing factor AIF [49]. Yu et al. administered intact mitochondria extracted from mouse livers into mice harboring subcutaneous and metastatic melanomas via the intravenous route. Transplantation of the healthy mitochondria induced cell cycle arrest and apoptosis by downregulating transcription of the anti-apoptotic protein BCL-2 and upregulating the mitochondria-associated apoptosis-inducing factor gene (Aifm3) transcripts. In addition, autophagy-related proteins such as LC3 were also upregulated at the transcriptional level. Finally, mitochondrial transplantation induced transcriptional silencing of proliferation-related and anti-apoptotic genes via histone methylation [50].
Hypoxia is one of the recognized hallmarks of cancer and contributes to the resistance of tumor cells to chemotherapy and radiotherapy. High glycolysis rates in hypoxic tumor cells support rapid tumor cell proliferation, and the metabolites create an acidic environment that is conducive to tumor growth [51][52]. Spees et al. treated A549 cells with ethidium bromide to induce mtDNA mutations and depletion and inhibit aerobic respiration. Following co-incubation of the mtDNA-depleted (A549ρ0) cells with human bone marrow-derived skin fibroblasts, the latter formed cytoplasmic extensions toward the target cells. Mitochondrial transplantation from the fibroblasts via these extensions restored oxidative phosphorylation in A549ρ0 cells, decreased the level of oxygen deprivation in the tumor cells, and attenuated the degree of malignancy [53].
In conclusion, mitochondrial transplantation has shown significant potential in the field of tumor therapy. Transplantation of healthy mitochondria into cancer cells can inhibit cell proliferation, enhance sensitivity to chemotherapy and radiation, and induce apoptosis. In addition, mitochondrial transplantation has been shown to rescue aerobic respiration and attenuate the Warburg effect in glioma and breast cancer cells, improve their radiosensitivity [44][54], induce apoptosis in melanoma cells, and inhibit lung cancer cells under hypoxic conditions [50][53]. These findings highlight the potential of mitochondrial transplantation as a novel tumor treatment strategy.

References

  1. Kaur, M.M.; Sharma, D.S. Mitochondrial repair as potential pharmacological target in cerebral ischemia. Mitochondrion 2022, 63, 23–31.
  2. Zhou, Y.; Danbolt, N.C. Glutamate as a neurotransmitter in the healthy brain. J. Neural. Transm. 2014, 121, 799–817.
  3. Hansen, K.B.; Yi, F.; Perszyk, R.E.; Furukawa, H.; Wollmuth, L.P.; Gibb, A.J.; Traynelis, S.F. Structure, function, and allosteric modulation of NMDA receptors. J. Gen. Physiol. 2018, 150, 1081–1105.
  4. Kang, J.B.; Park, D.J.; Shah, M.A.; Koh, P.O. Quercetin ameliorates glutamate toxicity-induced neuronal cell death by controlling calcium-binding protein parvalbumin. J. Vet. Sci. 2022, 23, e26.
  5. Kaza, A.K.; Wamala, I.; Friehs, I.; Kuebler, J.D.; Rathod, R.H.; Berra, I.; Ericsson, M.; Yao, R.; Thedsanamoorthy, J.K.; Zurakowski, D.; et al. Myocardial rescue with autologous mitochondrial transplantation in a porcine model of ischemia/reperfusion. J. Thorac. Cardiovasc. Surg. 2017, 153, 934–943.
  6. Orrenius, S.; Gogvadze, V.; Zhivotovsky, B. Calcium and mitochondria in the regulation of cell death. Biochem. Biophys. Res. Commun. 2015, 460, 72–81.
  7. Gong, Y.; Lin, J.; Ma, Z.; Yu, M.; Wang, M.; Lai, D.; Fu, G. Mitochondria-associated membrane-modulated Ca(2+) transfer: A potential treatment target in cardiac ischemia reperfusion injury and heart failure. Life Sci. 2021, 278, 119511.
  8. Hardingham, G.E. Coupling of the NMDA receptor to neuroprotective and neurodestructive events. Biochem. Soc. Trans. 2009, 37, 1147–1160.
  9. Zorov, D.B.; Juhaszova, M.; Sollott, S.J. Mitochondrial Reactive Oxygen Species (ROS) and ROS-Induced ROS Release. Physiol. Rev. 2014, 94, 909.
  10. Shanmughapriya, S.; Langford, D.; Natarajaseenivasan, K. Inter and Intracellular mitochondrial trafficking in health and disease. Ageing Res. Rev. 2020, 62, 101128.
  11. Pourmohammadi-Bejarpasi, Z.; Roushandeh, A.M.; Saberi, A.; Rostami, M.K.; Toosi, S.M.R.; Jahanian-Najafabadi, A.; Tomita, K.; Kuwahara, Y.; Sato, T.; Roudkenar, M.H. Mesenchymal stem cells-derived mitochondria transplantation mitigates I/R-induced injury, abolishes I/R-induced apoptosis, and restores motor function in acute ischemia stroke rat model. Brain Res. Bull. 2020, 165, 70–80.
  12. Zhang, Z.; Ma, Z.; Yan, C.; Pu, K.; Wu, M.; Bai, J.; Li, Y.; Wang, Q. Muscle-derived autologous mitochondrial transplantation: A novel strategy for treating cerebral ischemic injury. Behav. Brain Res. 2019, 356, 322–331.
  13. Ahmad, T.; Mukherjee, S.; Pattnaik, B.; Kumar, M.; Singh, S.; Kumar, M.; Rehman, R.; Tiwari, B.K.; Jha, K.A.; Barhanpurkar, A.P.; et al. Miro1 regulates intercellular mitochondrial transport & enhances mesenchymal stem cell rescue efficacy. EMBO J. 2014, 33, 994–1010.
  14. Tseng, N.; Lambie, S.C.; Huynh, C.Q.; Sanford, B.; Patel, M.; Herson, P.S.; Ormond, D.R. Mitochondrial transfer from mesenchymal stem cells improves neuronal metabolism after oxidant injury in vitro: The role of Miro1. J. Cereb. Blood Flow. Metab. 2021, 41, 761–770.
  15. Hayakawa, K.; Esposito, E.; Wang, X.; Terasaki, Y.; Liu, Y.; Xing, C.; Ji, X.; Lo, E.H. Transfer of mitochondria from astrocytes to neurons after stroke. Nature 2016, 535, 551–555.
  16. Li, H.; Wang, C.; He, T.; Zhao, T.; Chen, Y.Y.; Shen, Y.L.; Zhang, X.; Wang, L.L. Mitochondrial Transfer from Bone Marrow Mesenchymal Stem Cells to Motor Neurons in Spinal Cord Injury Rats via Gap Junction. Theranostics 2019, 9, 2017–2035.
  17. Berridge, M.V.; Neuzil, J. The mobility of mitochondria: Intercellular trafficking in health and disease. Clin. Exp. Pharmacol. Physiol. 2017, 44 (Suppl. 1), 15–20.
  18. Shin, B.; Cowan, D.B.; Emani, S.M.; Del Nido, P.J.; McCully, J.D. Mitochondrial Transplantation in Myocardial Ischemia and Reperfusion Injury. Adv. Exp. Med. Biol. 2017, 982, 595–619.
  19. Islam, M.N.; Das, S.R.; Emin, M.T.; Wei, M.; Sun, L.; Westphalen, K.; Rowlands, D.J.; Quadri, S.K.; Bhattacharya, S.; Bhattacharya, J. Mitochondrial transfer from bone-marrow-derived stromal cells to pulmonary alveoli protects against acute lung injury. Nat. Med. 2012, 18, 759–765.
  20. Tian, H.; Zhao, X.; Zhang, Y.; Xia, Z. Abnormalities of glucose and lipid metabolism in myocardial ischemia-reperfusion injury. Biomed. Pharmacother. 2023, 163, 114827.
  21. Zhang, Y.; Yu, Z.; Jiang, D.; Liang, X.; Liao, S.; Zhang, Z.; Yue, W.; Li, X.; Chiu, S.M.; Chai, Y.H.; et al. iPSC-MSCs with High Intrinsic MIRO1 and Sensitivity to TNF-α Yield Efficacious Mitochondrial Transfer to Rescue Anthracycline-Induced Cardiomyopathy. Stem Cell Rep. 2016, 7, 749–763.
  22. Sun, X.; Chen, H.; Gao, R.; Qu, Y.; Huang, Y.; Zhang, N.; Hu, S.; Fan, F.; Zou, Y.; Hu, K.; et al. Intravenous Transplantation of an Ischemic-specific Peptide-TPP-mitochondrial Compound Alleviates Myocardial Ischemic Reperfusion Injury. ACS Nano 2023, 17, 896–909.
  23. McCully, J.D.; Cowan, D.B.; Pacak, C.A.; Toumpoulis, I.K.; Dayalan, H.; Levitsky, S. Injection of isolated mitochondria during early reperfusion for cardioprotection. Am. J. Physiol. Heart Circ. Physiol. 2009, 296, H94–H105.
  24. Masuzawa, A.; Black, K.M.; Pacak, C.A.; Ericsson, M.; Barnett, R.J.; Drumm, C.; Seth, P.; Bloch, D.B.; Levitsky, S.; Cowan, D.B.; et al. Transplantation of autologously derived mitochondria protects the heart from ischemia-reperfusion injury. Am. J. Physiol. Heart Circ. Physiol. 2013, 304, H966–H982.
  25. McCully, J.D.; Levitsky, S.; Del Nido, P.J.; Cowan, D.B. Mitochondrial transplantation for therapeutic use. Clin. Transl. Med. 2016, 5, 16.
  26. Roche, S.; D’Ippolito, G.; Gomez, L.A.; Bouckenooghe, T.; Lehmann, S.; Montero-Menei, C.N.; Schiller, P.C. Comparative analysis of protein expression of three stem cell populations: Models of cytokine delivery system in vivo. Int. J. Pharm. 2013, 440, 72–82.
  27. Shen, Y.; Liu, X.; Shi, J.; Wu, X. Involvement of Nrf2 in myocardial ischemia and reperfusion injury. Int. J. Biol. Macromol. 2019, 125, 496–502.
  28. Somers, P.; Cornelissen, R.; Thierens, H.; Van Nooten, G. An optimized growth factor cocktail for ovine mesenchymal stem cells. Growth Factors 2012, 30, 37–48.
  29. De Miranda, M.C.; Rodrigues, M.A.; de Angelis Campos, A.C.; Faria, J.; Kunrath-Lima, M.; Mignery, G.A.; Schechtman, D.; Goes, A.M.; Nathanson, M.H.; Gomes, D.A. Epidermal growth factor (EGF) triggers nuclear calcium signaling through the intranuclear phospholipase Cδ-4 (PLCδ4). J. Biol. Chem. 2019, 294, 16650–16662.
  30. Schenk, S.; Mal, N.; Finan, A.; Zhang, M.; Kiedrowski, M.; Popovic, Z.; McCarthy, P.M.; Penn, M.S. Monocyte chemotactic protein-3 is a myocardial mesenchymal stem cell homing factor. Stem Cells 2007, 25, 245–251.
  31. Pacak, C.A.; Preble, J.M.; Kondo, H.; Seibel, P.; Levitsky, S.; Del Nido, P.J.; Cowan, D.B.; McCully, J.D. Actin-dependent mitochondrial internalization in cardiomyocytes: Evidence for rescue of mitochondrial function. Biol. Open 2015, 4, 622–626.
  32. Emani, S.M.; McCully, J.D. Mitochondrial transplantation: Applications for pediatric patients with congenital heart disease. Transl. Pediatr. 2018, 7, 169–175.
  33. Chen, K.; Lu, P.; Beeraka, N.M.; Sukocheva, O.A.; Madhunapantula, S.V.; Liu, J.; Sinelnikov, M.Y.; Nikolenko, V.N.; Bulygin, K.V.; Mikhaleva, L.M.; et al. Mitochondrial mutations and mitoepigenetics: Focus on regulation of oxidative stress-induced responses in breast cancers. Semin. Cancer Biol. 2022, 83, 556–569.
  34. Sies, H.; Jones, D.P. Reactive oxygen species (ROS) as pleiotropic physiological signalling agents. Nat. Rev. Mol. Cell Biol. 2020, 21, 363–383.
  35. Yang, Y.; Karakhanova, S.; Hartwig, W.; D’Haese, J.G.; Philippov, P.P.; Werner, J.; Bazhin, A.V. Mitochondria and Mitochondrial ROS in Cancer: Novel Targets for Anticancer Therapy. J. Cell Physiol. 2016, 231, 2570–2581.
  36. Yakes, F.M.; Van Houten, B. Mitochondrial DNA damage is more extensive and persists longer than nuclear DNA damage in human cells following oxidative stress. Proc. Natl. Acad. Sci. USA 1997, 94, 514–519.
  37. Zampieri, L.X.; Silva-Almeida, C.; Rondeau, J.D.; Sonveaux, P. Mitochondrial Transfer in Cancer: A Comprehensive Review. Int. J. Mol. Sci. 2021, 22, 3245.
  38. Wu, Z.; Wu, J.; Zhao, Q.; Fu, S.; Jin, J. Emerging roles of aerobic glycolysis in breast cancer. Clin. Transl. Oncol. 2020, 22, 631–646.
  39. Hanahan, D.; Weinberg, R.A. Hallmarks of cancer: The next generation. Cell 2011, 144, 646–674.
  40. Guerra, F.; Arbini, A.A.; Moro, L. Mitochondria and cancer chemoresistance. Biochim. Biophys. Acta Bioenerg. 2017, 1858, 686–699.
  41. Nile, D.L.; Rae, C.; Walker, D.J.; Waddington, J.C.; Vincent, I.; Burgess, K.; Gaze, M.N.; Mairs, R.J.; Chalmers, A.J. Inhibition of glycolysis and mitochondrial respiration promotes radiosensitisation of neuroblastoma and glioma cells. Cancer Metab. 2021, 9, 24.
  42. Fang, J.; Ma, Y.; Li, Y.; Li, J.; Zhang, X.; Han, X.; Ma, S.; Guan, F. CCT4 knockdown enhances the sensitivity of cisplatin by inhibiting glycolysis in human esophageal squamous cell carcinomas. Mol. Carcinog. 2022, 61, 1043–1055.
  43. Zhou, W.; Zhao, Z.; Yu, Z.; Hou, Y.; Keerthiga, R.; Fu, A. Mitochondrial transplantation therapy inhibits the proliferation of malignant hepatocellular carcinoma and its mechanism. Mitochondrion 2022, 65, 11–22.
  44. Sun, C.; Liu, X.; Wang, B.; Wang, Z.; Liu, Y.; Di, C.; Si, J.; Li, H.; Wu, Q.; Xu, D.; et al. Endocytosis-mediated mitochondrial transplantation: Transferring normal human astrocytic mitochondria into glioma cells rescues aerobic respiration and enhances radiosensitivity. Theranostics 2019, 9, 3595–3607.
  45. Astigiano, C.; Benzi, A.; Laugieri, M.E.; Piacente, F.; Sturla, L.; Guida, L.; Bruzzone, S.; De Flora, A. Paracrine ADP Ribosyl Cyclase-Mediated Regulation of Biological Processes. Cells 2022, 11, 2637.
  46. Li, J.P.; Wei, W.; Li, X.X.; Xu, M. Regulation of NLRP3 inflammasome by CD38 through cADPR-mediated Ca(2+) release in vascular smooth muscle cells in diabetic mice. Life Sci. 2020, 255, 117758.
  47. Takasawa, S. CD38-Cyclic ADP-Ribose Signal System in Physiology, Biochemistry, and Pathophysiology. Int. J. Mol. Sci. 2022, 23, 4306.
  48. Elliott, R.L.; Jiang, X.P.; Head, J.F. Mitochondria organelle transplantation: Introduction of normal epithelial mitochondria into human cancer cells inhibits proliferation and increases drug sensitivity. Breast Cancer Res. Treat. 2012, 136, 347–354.
  49. Chang, J.C.; Chang, H.S.; Wu, Y.C.; Cheng, W.L.; Lin, T.T.; Chang, H.J.; Kuo, S.J.; Chen, S.T.; Liu, C.S. Mitochondrial transplantation regulates antitumour activity, chemoresistance and mitochondrial dynamics in breast cancer. J. Exp. Clin. Cancer Res. 2019, 38, 30.
  50. Yu, Z.; Hou, Y.; Zhou, W.; Zhao, Z.; Liu, Z.; Fu, A. The effect of mitochondrial transplantation therapy from different gender on inhibiting cell proliferation of malignant melanoma. Int. J. Biol. Sci. 2021, 17, 2021–2033.
  51. Zhang, X.; Li, Y.; Ma, Y.; Yang, L.; Wang, T.; Meng, X.; Zong, Z.; Sun, X.; Hua, X.; Li, H. Yes-associated protein (YAP) binds to HIF-1α and sustains HIF-1α protein stability to promote hepatocellular carcinoma cell glycolysis under hypoxic stress. J. Exp. Clin. Cancer Res. 2018, 37, 216.
  52. Tian, H.; Zhu, X.; Lv, Y.; Jiao, Y.; Wang, G. Glucometabolic Reprogramming in the Hepatocellular Carcinoma Microenvironment: Cause and Effect. Cancer Manag. Res. 2020, 12, 5957–5974.
  53. Spees, J.L.; Olson, S.D.; Whitney, M.J.; Prockop, D.J. Mitochondrial transfer between cells can rescue aerobic respiration. Proc. Natl. Acad. Sci. USA 2006, 103, 1283–1288.
  54. Patel, P.S.; Castelow, C.; Patel, D.S.; Bhattacharya, S.K.; Kuscu, C.; Kuscu, C.; Makowski, L.; Eason, J.D.; Bajwa, A. Mitochondrial Role in Oncogenesis and Potential Chemotherapeutic Strategy of Mitochondrial Infusion in Breast Cancer. Int. J. Mol. Sci. 2022, 23, 12993.
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: Transplantation
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Cuilan Hu
,
Zheng Shi
,
Xiongxiong Liu
,
Chao Sun
View Times: 63
Revisions: 3 times (View History)
Update Date: 01 Feb 2024
Table of Contents
    1000/1000
    Hot Most Recent
    Feedback