Mitochondrial Transplantation and Transfer, from past to future expectations

Öz

Mitochondria, with their unique roles in cell energy metabolism, continue to be studied by years of research. Mitochondrial transfer can be summarized as the process of transferring isolated mitochondria to the damaged tissue. In this way, it is aimed to improve the mitochondrial dysfunction in areas with impaired mitochondrial functions such as heart damaged tissue. Although there are many studies on this subject, especially cardiomyocytes, the protective effects of the application in processes such as myocardial ischemia and reperfusion injury continues to be investigated. Although there are different procedures for transferring the isolated mitochondrin to the damaged tissue, many studies have reported positive results regarding the application. In this review, it is aimed to look at the subject from a wide window, while examining the studies done in this field in the literature.

Anahtar Kelimeler

• Mitochondrial transfer
• Mitochondrial transplantation
• Mitochondria

Mitokondri Nakli ve Transferi, geçmişten gelecek beklentilere

Öz

Hücre enerji eldesinde üstlendikleri eşsiz rolleri ile mitokondri yıllardır devam eden araştırmalar ile incelenmeye devam etmektedir. Mitokondriyal transfer hasarlanmış dokuya izole edilmiş olan mitokondrinin transfer edilme süreci olarak özetlenebilir. Bu sayede kalp hasarı olan doku gibi mitokondrial fonksiyonları bozulmuş bölgede mitokondrial disfonksiyon durmunun düzeltilmesi amaçlanmaktadır. Bu konu ile ilgili özellikle kalp dokusunda birçok çalışma olmakla beraber uygulanın miyokardial iskemi, reperfüzyon hasarı gibi süreçlerde koruyucu etkinliği araştırılmaya devam etmektedir. İzole edilen mitokondrin hasarlı dokuya aktarılmasında farklı prosedürler bulunmakla birlikte, birçok çalışmada uygulama ile ilgili olumlu sonuçlar bildirlmektedir. Derlemede literatürde bu alanda yapılmış olan çalışmalar incelenmekle birlikte konuya geniş bir penceren bakılması hedeflenmiştir.

Anahtar Kelimeler

• Mitokondriyal transfer
• Mitokondriyal transplantasyon
• Mitokondri

Kaynakça

1. 1. Zhou M, Yu Y, Luo Y, Luo X, Zhang Y, Zhou X, et al. Mitochondrial Transplantation: A Unique Treatment Strategy. Journal of Cardiovascular Pharmacology. 2022;79(6):759-68.
2. 2. McCully JD, Cowan DB, Pacak CA, Toumpoulis IK, Dayalan H, Levitsky S. Injection of isolated mitochondria during early reperfusion for cardioprotection. American Journal of Physiology-Heart and Circulatory Physiology. 2009;296(1):H94-H105.
3. 3. Masuzawa A, Black KM, Pacak CA, Ericsson M, Barnett RJ, Drumm C, et al. Transplantation of autologously derived mitochondria protects the heart from ischemia-reperfusion injury. American Journal of Physiology-Heart and Circulatory Physiology. 2013;304(7):H966-H82.
4. 4. Kitani T, Kami D, Matoba S, Gojo S. Internalization of isolated functional mitochondria: involvement of macropinocytosis. Journal of cellular and molecular medicine. 2014;18(8):1694-703.
5. 5. Ali Pour P, Kenney MC, Kheradvar A. Bioenergetics consequences of mitochondrial transplantation in cardiomyocytes. Journal of the American Heart Association. 2020;9(7):e014501.
6. 6. Kaza AK, Wamala I, Friehs I, Kuebler JD, Rathod RH, Berra I, et al. Myocardial rescue with autologous mitochondrial transplantation in a porcine model of ischemia/reperfusion. The Journal of thoracic and cardiovascular surgery. 2017;153(4):934-43.
7. 7. Cowan DB, Yao R, Akurathi V, Snay ER, Thedsanamoorthy JK, Zurakowski D, et al. Intracoronary delivery of mitochondria to the ischemic heart for cardioprotection. PloS one. 2016;11(8):e0160889.
8. 8. Chernyak B. Mitochondrial transplantation: a critical analysis. Biochemistry (Moscow). 2020;85:636-41.

9. 9. Emani SM, Piekarski BL, Harrild D, Pedro J, McCully JD. Autologous mitochondrial transplantation for dysfunction after ischemia-reperfusion injury. The Journal of thoracic and cardiovascular surgery. 2017;154(1):286-9.
10. 10. Blitzer D, Guariento A, Doulamis IP, Shin B, Moskowitzova K, Barbieri GR, et al. Delayed transplantation of autologous mitochondria for cardioprotection in a porcine model. The Annals of Thoracic Surgery. 2020;109(3):711-9.
11. 11. Guariento A, Blitzer D, Doulamis I, Shin B, Moskowitzova K, Orfany A, et al. Preischemic autologous mitochondrial transplantation by intracoronary injection for myocardial protection. The Journal of thoracic and cardiovascular surgery. 2020;160(2):e15-e29.
12. 12. McCully JD, Levitsky S, Del Nido PJ, Cowan DB. Mitochondrial transplantation for therapeutic use. Clinical and translational medicine. 2016;5:1-13.
13. 13. McCully JD, Cowan DB, Emani SM, Pedro J. Mitochondrial transplantation: from animal models to clinical use in humans. Mitochondrion. 2017;34:127-34.
14. 14. Orfany A, Arriola CG, Doulamis IP, Guariento A, Ramirez-Barbieri G, Moskowitzova K, et al. Mitochondrial transplantation ameliorates acute limb ischemia. Journal of Vascular Surgery. 2020;71(3):1014-26.
15. 15. Chang J-C, Liu K-H, Chuang C-S, Su H-L, Wei Y-H, Kuo S-J, et al. Treatment of human cells derived from MERRF syndrome by peptide-mediated mitochondrial delivery. Cytotherapy. 2013;15(12):1580-96.
16. 16. Quintero OA, DiVito MM, Adikes RC, Kortan MB, Case LB, Lier AJ, et al. Human Myo19 is a novel myosin that associates with mitochondria. Current Biology. 2009;19(23):2008-13.
17. 17. Ahmad T, Mukherjee S, Pattnaik B, Kumar M, Singh S, Kumar M, et al. Miro1 regulates intercellular mitochondrial transport & enhances mesenchymal stem cell rescue efficacy. The EMBO journal. 2014;33(9):994-1010.
18. 18. Li H, Wang C, He T, Zhao T, Chen Y-y, Shen Y-l, et al. Mitochondrial transfer from bone marrow mesenchymal stem cells to motor neurons in spinal cord injury rats via gap junction. Theranostics. 2019;9(7):2017.
19. 19. Yamada Y, Ito M, Arai M, Hibino M, Tsujioka T, Harashima H. Challenges in promoting mitochondrial transplantation therapy. International Journal of Molecular Sciences. 2020;21(17):6365.
20. 20. Chang J-C, Wu S-L, Liu K-H, Chen Y-H, Chuang C-S, Cheng F-C, et al. Allogeneic/xenogeneic transplantation of peptide-labeled mitochondria in Parkinson's disease: restoration of mitochondria functions and attenuation of 6-hydroxydopamine–induced neurotoxicity. Translational Research. 2016;170:40-56. e3.
21. 21. Chang J-C, Chang H-S, Wu Y-C, Cheng W-L, Lin T-T, Chang H-J, et al. Mitochondrial transplantation regulates antitumour activity, chemoresistance and mitochondrial dynamics in breast cancer. Journal of Experimental & Clinical Cancer Research. 2019;38(1):1-16.
22. 22. Doulamis IP, Guariento A, Duignan T, Orfany A, Kido T, Zurakowski D, et al. Mitochondrial transplantation for myocardial protection in diabetic hearts. European Journal of Cardio-Thoracic Surgery. 2020;57(5):836-45.
23. 23. Lin H-C, Liu S-Y, Lai H-S, Lai I-R. Isolated mitochondria infusion mitigates ischemia-reperfusion injury of the liver in rats. Shock. 2013;39(3):304-10.
24. 24. Fu A, Shi X, Zhang H, Fu B. Mitotherapy for fatty liver by intravenous administration of exogenous mitochondria in male mice. Frontiers in pharmacology. 2017;8:241.
25. 25. Moskowitzova K, Orfany A, Liu K, Ramirez-Barbieri G, Thedsanamoorthy JK, Yao R, et al. Mitochondrial transplantation enhances murine lung viability and recovery after ischemia-reperfusion injury. American Journal of Physiology-Lung Cellular and Molecular Physiology. 2020;318(1):L78-L88.
26. 26. Islam MN, Das SR, Emin MT, Wei M, Sun L, Westphalen K, et al. Mitochondrial transfer from bone-marrow–derived stromal cells to pulmonary alveoli protects against acute lung injury. Nature medicine. 2012;18(5):759-65.
27. 27. Zhu L, Zhang J, Zhou J, Lu Y, Huang S, Xiao R, et al. Mitochondrial transplantation attenuates hypoxic pulmonary hypertension. Oncotarget. 2016;7(31):48925.
28. 28. Gollihue JL, Patel SP, Eldahan KC, Cox DH, Donahue RR, Taylor BK, et al. Effects of mitochondrial transplantation on bioenergetics, cellular incorporation, and functional recovery after spinal cord injury. Journal of neurotrauma. 2018;35(15):1800-18.
29. 29. Pourmohammadi-Bejarpasi Z, Roushandeh AM, Saberi A, Rostami MK, Toosi SMR, Jahanian-Najafabadi A, et al. 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 Research Bulletin. 2020;165:70-80.
30. 30. Heyck M, Bonsack B, Zhang H, Sadanandan N, Cozene B, Kingsbury C, et al. The brain and eye: treating cerebral and retinal ischemia through mitochondrial transfer. Experimental Biology and Medicine. 2019;244(16):1485-92.
31. 31. Jiang D, Gao F, Zhang Y, Wong DSH, Li Q, Tse H-f, et al. Mitochondrial transfer of mesenchymal stem cells effectively protects corneal epithelial cells from mitochondrial damage. Cell death & disease. 2016;7(11):e2467-e.
32. 32. Wang Y, Ni J, Gao C, Xie L, Zhai L, Cui G, et al. Mitochondrial transplantation attenuates lipopolysaccharide-induced depression-like behaviors. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2019;93:240-9.
33. 33. Kubat GB, Ozler M, Ulger O, Ekinci O, Atalay O, Celik E, et al. The effects of mesenchymal stem cell mitochondrial transplantation on doxorubicin‐mediated nephrotoxicity in rats. Journal of biochemical and molecular toxicology. 2021;35(1):e22612.
34. 34. Oktay K, Baltaci V, Sonmezer M, Turan V, Unsal E, Baltaci A, et al. Oogonial precursor cell-derived autologous mitochondria injection to improve outcomes in women with multiple IVF failures due to low oocyte quality: a clinical translation. Reproductive Sciences. 2015;22:1612-7.
35. 35. Kong L, Liu Z, Li H, Zhu L, Chen S, Xing F. First twins born in Mainland China by autologous granular cell mitochondria transfer. Di 1 jun yi da xue xue bao= Academic Journal of the First Medical College of PLA. 2003;23(9):990-1.
36. 36. Hwang JW, Lee MJ, Chung TN, Lee HAR, Lee JH, Choi SY, et al. The immune modulatory effects of mitochondrial transplantation on cecal slurry model in rat. Critical Care. 2021;25(1):1-12.
37. 37. Zhou J, Zhang J, Lu Y, Huang S, Xiao R, Zeng X, et al. Mitochondrial transplantation attenuates hypoxic pulmonary vasoconstriction. Oncotarget. 2016;7(21):31284.
38. 38. Robicsek O, Ene HM, Karry R, Ytzhaki O, Asor E, McPhie D, et al. Isolated mitochondria transfer improves neuronal differentiation of schizophrenia-derived induced pluripotent stem cells and rescues deficits in a rat model of the disorder. Schizophrenia bulletin. 2018;44(2):432-42.
39. 39. Bertero E, Maack C, O’Rourke B. Mitochondrial transplantation in humans:“magical” cure or cause for concern? The Journal of clinical investigation. 2018;128(12):5191-4.
40. 40. Bertero E, O’Rourke B, Maack C. Mitochondria do not survive calcium overload during transplantation. Circulation research. 2020;126(6):784-6.
41. 41. Pacak CA, Preble JM, Kondo H, Seibel P, Levitsky S, Del Nido PJ, et al. Actin-dependent mitochondrial internalization in cardiomyocytes: evidence for rescue of mitochondrial function. Biology open. 2015;4(5):622-6.
42. 42. Terrovitis J, Stuber M, Youssef A, Preece S, Leppo M, Kizana E, et al. Magnetic resonance imaging overestimates ferumoxide-labeled stem cell survival after transplantation in the heart. Circulation. 2008;117(12):1555-62.
43. 43. Clark MA, Shay JW. Mitochondrial transformation of mammalian cells. Nature. 1982;295:605-7.
44. 44. Ramirez-Barbieri G, Moskowitzova K, Shin B, Blitzer D, Orfany A, Guariento A, et al. Alloreactivity and allorecognition of syngeneic and allogeneic mitochondria. Mitochondrion. 2019;46:103-15.