Mitochondrial remodeling under hypoxia

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Abstract

Mitochondria are dynamic organelles capable of undergoing fission and fusion in response to the cell’s metabolic demands. These processes, collectively referred to as mitochondrial remodeling, determine the number, shape, and size of mitochondria within the cell. In recent decades, there has been growing interest in elucidating the mechanisms regulating mitochondrial dynamics under both physiological and pathological conditions. Regulatory proteins responsible for the fission and fusion of mitochondrial membranes have been identified and are activated in response to the cell’s energy demands. An imbalance between these processes disrupts cellular metabolism, impairs numerous cellular functions and adaptive capacity. Increasing evidence suggests that hypoxia significantly influences mitochondrial remodeling, with most studies focusing on the relationship between acute hypoxia and the expression levels of key fission and fusion regulatory proteins.

The aim of this article is to review the current literature on the effects of hypoxia on mitochondrial changes in both embryonic and adult tissues and to discuss the prospects for further research on mitochondrial remodeling mechanisms under reduced oxygen conditions.

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About the authors

Kristina A. Skvortsova

Research Center of Neurology; The Russian National Research Medical University named after N.I. Pirogov

Author for correspondence.
Email: Skvortsova_ka@mail.ru
ORCID iD: 0009-0000-2413-0262
SPIN-code: 1350-7458
Russian Federation, 5 Obukha aly, bldg 2, 105064, Moscow; Moscow

Tatiana I. Baranich

Research Center of Neurology; The Russian National Research Medical University named after N.I. Pirogov

Email: baranich_tatyana@mail.ru
ORCID iD: 0000-0002-8999-9986
SPIN-code: 9325-2229

Cand. Sci. (Medicine)

Russian Federation, 5 Obukha aly, bldg 2, 105064, Moscow; Moscow

Zainab M. Omarova

The Russian National Research Medical University named after N.I. Pirogov

Email: Zaika540000@mail.ru
ORCID iD: 0009-0004-6719-4775
Russian Federation, Moscow

Dmitry A. Kharlamov

V.F. Voyno-Yasenetsky Scientific and Practical Center of Specialized Medical Care for Children

Email: dmitoch@gmail.ru
ORCID iD: 0009-0007-5533-084X
SPIN-code: 5624-3488

Cand. Sci. (Medicine)

Russian Federation, Moscow

Irina A. Bicherova

The Russian National Research Medical University named after N.I. Pirogov

Email: raddp8@yandex.ru
ORCID iD: 0009-0007-1454-0461
SPIN-code: 4817-2690

Cand. Sci. (Medicine)

Russian Federation, Moscow

Valeria V. Glinkina

The Russian National Research Medical University named after N.I. Pirogov

Email: vglinkina@mail.ru
ORCID iD: 0000-0001-8708-6940
SPIN-code: 4425-5052

Dr. Sci. (Medicine), Professor

Russian Federation, Moscow

Vladimir S. Sukhorukov

Research Center of Neurology; The Russian National Research Medical University named after N.I. Pirogov

Email: vsukhorukov@gmail.com
ORCID iD: 0000-0002-0552-6939
SPIN-code: 1112-4406

Dr. Sci. (Medicine), Professor

Russian Federation, 5 Obukha aly, bldg 2, 105064, Moscow; Moscow

References

  1. Monzel AS, Enríquez JA, Picard M. Multifaceted mitochondria: moving mitochondrial science beyond function and dysfunction. Nat Metab. 2023;5(4):546–562. doi: 10.1038/s42255-023-00783-1
  2. Lewis MR, Lewis WH. Mitochondria in tissue culture. Science. 1914;39(1000):330–333. doi: 10.1126/science.39.1000.330
  3. Sukhorukov VS. Some biomedical aspects of mitochondrial dynamics. In: Questions of morphology of the XXI century: Proceedings of the 26th All-Russian Scientific Conference, Saint Petersburg, 16-17 May 2024. Saint Petersburg: Limited Liability Company «Izdatel’stvo DEAN», 2024. P. 62–75. EDN: RNJJGD
  4. Sukhorukov VS, Baranich TI, Egorova AV, et al. Mitochondrial dynamics and the significance of its disturbances in the development of childhood diseases. Part I. Physiological and neurological aspects. Russian Bulletin of Perinatology and Pediatrics. 2024;69(1):25–33. doi: 10.21508/1027-4065-2024-69-1-25-33 EDN: VUWYOY
  5. Sukhorukov VS, Baranich TI, Egorova AV, et al. Mitochondrial dynamics and the significance of its disturbances in the development of childhood diseases. Part II. Cardiological and endocrinological aspects. Russian Bulletin of Perinatology and Pediatrics. 2024;69(2):12–18. doi: 10.21508/1027-4065-2024-69-2-12-18 EDN: HDSWRI
  6. Adebayo M, Singh S, Singh AP, Dasgupta S. Mitochondrial fusion and fission: The fine-tune balance for cellular homeostasis. FASEB J. 2021;35(6):e21620. doi: 10.1096/fj.202100067R
  7. Chen W, Zhao H, Li Y. Mitochondrial dynamics in health and disease: mechanisms and potential targets. Signal Transduct Target Ther. 2023;8(1):333. doi: 10.1038/s41392-023-01547-9
  8. Sun F, Fang M, Zhang H, et al. Drp1: Focus on Diseases Triggered by the Mitochondrial Pathway. Cell Biochem Biophys. 2024;82(2):435–455. doi: 10.1007/s12013-024-01245-5
  9. Tilokani L, Nagashima S, Paupe V, Prudent J. Mitochondrial dynamics: overview of molecular mechanisms. Essays Biochem. 2018;62(3):341–360. doi: 10.1042/EBC20170104
  10. Kleele T, Rey T, Winter J, et al. Distinct fission signatures predict mitochondrial degradation or biogenesis. Nature. 2021;593(7859):435–439. doi: 10.1038/s41586-021-03510-6
  11. Breitzig MT, Alleyn MD, Lockey RF, Kalliputi N. A mitochondrial delicacy: dynamin-related protein 1 and mitochondrial dynamics. Am J Physiol Cell Physiol. 2018;315(1):C80–C90. doi: 10.1152/ajpcell.00042.2018
  12. Murata D, Arai K, Iijima M, Sesaki H. Mitochondrial division, fusion and degradation. J Biochem. 2020;167(3):233–241. doi: 10.1093/jb/mvz106
  13. Sukhorukov VS, Voronkova AS, Baranich TI, et al. Molecular Mechanisms of Interactions between Mitochondria and the Endoplasmic Reticulum: A New Look at How Important Cell Functions are Supported. Molecular Biology. 2022;56(1):59–71. doi: 10.1134/S0026893322010071 EDN: GTPNFD
  14. Song Z, Chen H, Fiket M, et al. OPA1 processing controls mitochondrial fusion and is regulated by mRNA splicing, membrane potential, and Yme1L. J Cell Biol. 2007;178(5):749–755. doi: 10.1083/jcb.200704110
  15. Wakabayashi J, Zhang Z, Wakabayashi N, et al. The dynamin-related GTPase Drp1 is required for embryonic and brain development in mice. J Cell Biol. 2009;186(6):805–816. doi: 10.1083/jcb.200903065
  16. Chen H, Detmer SA, Ewald AJ, et al. Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development. J Cell Biol. 2003;160(2):189–200. doi: 10.1083/jcb.200211046
  17. Hamze C. Mitofusin 1 and Mitofusin 2 Function in the Context of Brain Development [dissertation]. Ottawa; 2011. Available from: http://dx.doi.org/10.20381/ruor-4991935d-4688-a8af-6a40c846ed67
  18. Chen H, Ren S, Clish C, et al. Titration of mitochondrial fusion rescues Mff-deficient cardiomyopathy. J Cell Biol. 2015;211(4):795–805. doi: 10.1083/jcb.201507035
  19. Liu X, Song L, Yu J, et al. Mdivi-1: a promising drug and its underlying mechanisms in the treatment of neurodegenerative diseases. Histol Histopathol. 2022;37(6):505–512. doi: 10.14670/HH-18-443
  20. Ding J, Zhang Z, Li S, et al. Mdivi-1 alleviates cardiac fibrosis post myocardial infarction at infarcted border zone, possibly via inhibition of Drp1-Activated mitochondrial fission and oxidative stress. Arch Biochem Biophys. 2022;718:109147. doi: 10.1016/j.abb.2022.109147
  21. Li L, Mu Z, Liu P, et al. Mdivi-1 alleviates atopic dermatitis through the inhibition of NLRP3 inflammasome. Exp Dermatol. 2021;30(12):1734–1744. doi: 10.1111/exd.14412
  22. Su ZD, Li CQ, Wang HW, et al. Inhibition of DRP1-dependent mitochondrial fission by Mdivi-1 alleviates atherosclerosis through the modulation of M1 polarization. J Transl Med. 2023;21(1):427. doi: 10.1186/s12967-023-04270-9
  23. Fedorova EN, Egorova AV, Voronkov DN et al. DRP1 Regulation as a Potential Target in Hypoxia-Induced Cerebral Pathology. J Mol Pathol. 2023;4(4):333–348. doi: 10.3390/jmp4040027
  24. Xin Y, Zhao L, Peng R. HIF-1 signaling: an emerging mechanism for mitochondrial dynamics. J Physiol Biochem. 2023;79(3):489–500. doi: 10.1007/s13105-023-00966-0
  25. Baranich TI, Voronkova AS, Anufriev PL, et al. Hypoxia-inducible Factors–Their Regulation and Function in Neural Tissue. Human Physiology. 2020;46(8):895–899. doi: 10.1134/S0362119720080022
  26. Loboda A, Jozkowicz A, Dulak J. HIF-1 and HIF-2 transcription factors--similar but not identical. Mol Cells. 2010;29(5):435–442. doi: 10.1007/s10059-010-0067-2
  27. Yang C, Zhong ZF, Wang SP, et al. HIF-1: structure, biology and natural modulators. Chin J Nat Med. 2021;19(7):521–527. doi: 10.1016/S1875-5364(21)60051-1
  28. Zhao JF, Rodger CE, Allen GFG., et al. HIF1α-dependent mitophagy facilitates cardiomyoblast differentiation. Cell Stress. 2020;4(5):99–113. doi: 10.15698/cst2020.05.220
  29. Fajersztajn L, Veras MM. Hypoxia: From Placental Development to Fetal Programming. Birth Defects Res. 2017;109(17):1377–1385. doi: 10.1002/bdr2.1142
  30. Gillmore T, Farrell A, Alahari S. et al. Dichotomy in hypoxia-induced mitochondrial fission in placental mesenchymal cells during development and preeclampsia: consequences for trophoblast mitochondrial homeostasis. Cell Death Dis. 2022;13(2):191. doi: 10.1038/s41419-022-04641-y
  31. Wang B, Zeng H, Liu J, Sun M. Effects of Prenatal Hypoxia on Nervous System Development and Related Diseases. Front Neurosci. 2021;15:755554. doi: 10.3389/fnins.2021.755554
  32. Quebedeaux TM, Song H, Giwa-Otusajo J, Thompson LP. Chronic Hypoxia Inhibits Respiratory Complex IV Activity and Disrupts Mitochondrial Dynamics in the Fetal Guinea Pig Forebrain. Reprod Sci. 2022;29(1):184–192. doi: 10.1007/s43032-021-00779-w
  33. Han J, Tao W, Cui W, Chen J. Propofol via Antioxidant Property Attenuated Hypoxia-Mediated Mitochondrial Dynamic Imbalance and Malfunction in Primary Rat Hippocampal Neurons. Oxid Med Cell Longev. 2022;2022:6298786. doi: 10.1155/2022/6298786
  34. Jain K, Prasad D, Singh SB, Kohli E. Hypobaric Hypoxia Imbalances Mitochondrial Dynamics in Rat Brain Hippocampus. Neurol Res Int. 2015;2015:742059. doi: 10.1155/2015/742059
  35. Tajsic T, Morrell NW. Smooth muscle cell hypertrophy, proliferation, migration and apoptosis in pulmonary hypertension. Compr Physiol. 2011;1(1):295–317. doi: 10.1002/cphy.c100026
  36. Chen X, Yao JM, Fang X, et al. Hypoxia promotes pulmonary vascular remodeling via HIF-1α to regulate mitochondrial dynamics. J Geriatr Cardiol. 2019;16(12):855–871. doi: 10.11909/j.issn.1671-5411.2019.12.003
  37. Nishimura A, Shimauchi T, Tanaka T, et al. Hypoxia-induced interaction of filamin with Drp1 causes mitochondrial hyperfission-associated myocardial senescence. Sci Signal. 2018;11(556):eaat5185. doi: 10.1126/scisignal.aat5185
  38. Ong SB, Subrayan S, Lim SY, et al. Inhibiting mitochondrial fission protects the heart against ischemia/reperfusion injury. Circulation. 2010;121(18):2012–2022. doi: 10.1161/CIRCULATIONAHA.109.906610
  39. Sharp WW, Fang YH, Han M, et al. Dynamin-related protein 1 (Drp1)-mediated diastolic dysfunction in myocardial ischemia-reperfusion injury: therapeutic benefits of Drp1 inhibition to reduce mitochondrial fission. FASEB J. 2014;28(1):316–326. doi: 10.1096/fj.12-226225
  40. Piao L, Fang YH, Fisher M, et al. Dynamin-related protein 1 is a critical regulator of mitochondrial calcium homeostasis during myocardial ischemia/reperfusion injury. FASEB J. 2024;38(1):e23379. doi: 10.1096/fj.202301040RR
  41. Niu X, Zhang J, Hu S, et al. lncRNA Oip5-as1 inhibits excessive mitochondrial fission in myocardial ischemia/reperfusion injury by modulating DRP1 phosphorylation. Cell Mol Biol. 2024;29(1):72. doi: 10.1186/s11658-024-00588-4
  42. Kirshenbaum LA, Dhingra R, Bravo-Sagua R, Lavandero S. DIAPH1-MFN2 interaction decreases the endoplasmic reticulum-mitochondrial distance and promotes cardiac injury following myocardial ischemia. Nat Commun. 2024;15(1):1469. doi: 10.1038/s41467-024-45560-0
  43. Madhu V, Boneski PK, Silagi E, et al. Hypoxic Regulation of Mitochondrial Metabolism and Mitophagy in Nucleus Pulposus Cells Is Dependent on HIF-1α-BNIP3 Axis. J Bone Miner Res. 2020;35(8):1504–1524. doi: 10.1002/jbmr.4019
  44. Sun H, Li X, Chen X, et al. Drp1 activates ROS/HIF-1α/EZH2 and triggers mitochondrial fragmentation to deteriorate hypercalcemia-associated neuronal injury in mouse model of chronic kidney disease. J Neuroinflammation. 2022;19(1):213. doi: 10.1186/s12974-022-02542-7

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2. Fig. 1. Diagram illustrating the increased activity of mitochondrial fission upon HIF-1 stabilization: HIF-1a and HIF-1b (Hypoxia-Inducible Factor 1 alpha and beta), transcriptional regulators of metabolic adaptation to oxygen level changes in the cell; DRP1 (Dynamin-Related Protein 1), a mitochondrial fission activator protein; OPA1 (Optic Atrophy 1), a mitochondrial fusion activator protein; MFN1, 2 (Mitofusin 1 and 2), mitofusin proteins; Mff (Mitochondrial Fission Factor), MID (Mitochondrial Dynamics Proteins), regulatory proteins involved in the recruitment of DRP1 to mitochondrial fission sites; Fis1 (Fission 1), a protein mediating the interaction of the detached mitochondrial fragment with the lysosome for degradation. Figure created by the authors.

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