Yu.A. Cheremnov1, V.N. Davidenko2, V.V. Alekseev3, L.I. Markvo4, Yu.N. Korolev5, N.V. Alexeeva6, N.V. Shatunova7

1–7 FSBEUI HME “Rostov State Medical University”, Ministry of Health of the Russian Federation (Rostov-on-Don, Russia)

1 ury369@yandex.ru, 2 davidenko-116@yandex.ru, 3 аlekseev_vv@rostgmu.ru, 4 mark-wo@yandex.ru, 5 korol-lev63@mail.ru, 6 аlekseeva_nv@rostgmu.ru, 7 shatunova_nv@rostgmu.ru

The mitochondrion is a double-membrane, semi-autonomous organelle that is an essential component of the eukaryotic cell. Mitochondria were first described in the 19th century, and with the advent of new research methods in the 20th century, their primary function—energy production—was determined. However, over the years, through mitochondrial research, specialists have increasingly uncovered the organelle's fundamental functions.

The aim of this study is to analyze the stages of mitochondrial study, to better understand the ultrastructural features and functional loads of these essential intracellular structures, and the morphofunctional changes that occur in pathology.

This article describes the stages of mitochondrial study: microscopic, histochemical, biochemical, electron microscopic, and genetic. The principle by which mitochondrial study can be divided into stages is based on the invention of new research methods, each of which has allowed for the elucidation of specific functions or ultrastructural features of the organelle. Both classical and non-classical functions of mitochondria are also discussed. Specifically, their role in heat production, steroidogenesis, iron metabolism, cell apoptosis, activation of immune responses, and the release of neurotransmitters and secretory vesicles containing hormones.

Extensive knowledge of the role of this organelle in the cell can serve as a tool for understanding the pathogenesis of numerous pathologies in which mitochondrial function or structure are altered, as well as opening up new avenues for the application of this knowledge in medicine.

Cheremnov Yu.A., Davidenko V.N., Alekseev V.V., Markvo L.I., Korolev Yu.N., Alexeeva N.V., Shatunova N.V. Mitochondria as one of the most important organelles of the cell. Technologies of Living Systems. 2026. V. 23. № 3. Р. 48-58. DOI: https://doi.org/ 10.18127/j20700997-202603-05 (In Russian).

1. Frelikh G.A., Polomeeva N.Yu., Vasil'ev A.S., Udat V.V. Sovremennye metody otsenki funktsional'nogo sostoyaniya mitokhondriy. Sibirskiy zhurnal klinicheskoy i eksperimental'noy meditsiny. 2013. T. 28. № 3. S. 7–13. (in Russian).
2. Leninger A.L. Mitokhondriya: Molekulyarnye osnovy struktury i funktsii. M.: Mir. 1966. 316 s. (in Russian).
3. Panov A.V., Dikalov S.I., Darenskaya M.A. i dr. Mitokhondrii: starenie, metabolicheskiy sindrom i serdechno-sosudistaya patologiya. Stanovlenie novoy paradigmy. Acta Biomedica Scientifica. 2020. T. 5. № 4. S. 33–44. (in Russian).
4. Muranova A.V., Strokov I.A. Mitokhondrial'nye tsitopatii: sindromy melas i MIDD. Odin geneticheskiy defekt – raznye klinicheskie fenotipy. Nevrologicheskiy zhurnal. 2017. № 1. S. 19–24. (in Russian).
5. Fomchenko N.E., Voropaev E.V., Skachkov A.V., Zatora N.Yu. Biologicheskaya rol' mitokhondriy v starenii organizma. Problemy zdorov'ya i ekologii. 2015. № 4. S. 8–13. (in Russian).
6. Merezhkovskiy K.S. Teoriya dvukh plazm kak osnova simbiogenezisa, novogo ucheniya o proiskhozhdenii organizmov. Kazan': Tipo-lit. Imp. Un-ta. 1909. 102 s. (in Russian).
7. Panov A.V., Golubenko M.V., Darenskaya M.A., Kolesnikov S.I. Proiskhozhdenie mitokhondriy i ikh rol' v evolyutsii zhizni i zdorov'ya cheloveka. Acta Biomedica Scientifica. 2020. T. 5. № 5. S. 12–25. (in Russian).
8. Ruina E.A., Chadayeva O.I., Parshina E.V., Smirnov A.A. Opticheskaya nevropatiya Lebera. Meditsinskiy al'manakh. 2017. № 5. S. 120–126. (in Russian).
9. Alvarez-Delgado V. Carolina, Mendoza-Rodríguez C. Adriana, Picazo O., Cerbón M. Different expression of alpha and beta mitochondrial estrogen receptors in the aging rat brain: interaction with respiratory complex. Experimental Gerontology. 2010. № 45. P. 580–585.
10. Murzaeva M.V. Biologicheskaya rol' mitokhondriy v usloviyakh normy i patologii. Byulleten' meditsinskikh internet-konferentsiy. 2018. T. 8. № 9. S. 422. (in Russian).
11. Mao W., Yu X.X., Zhong A. et al. UCP4, a novel brain-specific mitochondrial protein that reduces membrane potential in mammalian cells. FEBS Lett. 1999. V. 443. № 3. P. 326-330.
12. Kern B., Ivanina A.V., Piontkivska H. et al. Molecular characterization and expression of a novel homolog of uncoupling protein 5 (UCP5) from the eastern oyster Crassostrea virginica (Bivalvia: Ostreidae). Comp. Biochem. Physiol. Part D Genomics Proteomics. 2009. V. 4. № 2. P. 121-127. DOI: 10.1016/j.cbd.2008.12.006
13. Bakhtyukov A.A., Shpakov A.O. Molekulyarnye mekhanizmy regulyatsii steroidogeneza v kletkakh Leydiga. Tsitologiya. 2016. T. 58. № 9. P. 666–678. (in Russian).
14. Midzak A., Papadopoulos V. Adrenal mitochondria and steroidogenesis: from individual proteins to functional protein assemblies. Front. Endocrinol. (Lausanne). 2016. V. 7. P. 106. DOI: 10.3389/fendo.2016.00106
15. Kit O.I., Frantsiyants E.M., Neskubina I.V. i dr. Vliyanie varianta razvitiya melanomy V16/F10 na soderzhanie kal'tsiya v mitokhondriyakh razlichnykh organov samok myshey. Issledovaniya i praktika v meditsine. 2021. V. 8. № 1. P. 20–29. (in Russian).
16. Agarwal A., Wu P.H., Hughes E.G. et al. Transient opening of the mitochondrial permeability transition pore induces microdomain calcium transients in astrocyte processes. Neuron. 2017. V. 93. № 3. P. 587–605.
17. Bauer T.M., Murphy E. Role of Mitochondrial Calcium and the Permeability Transition Pore in Regulating Cell Death. Circ. Res. 2020. V. 126. № 2. P. 280–293. DOI: 10.1161/CIRCRESAHA.119.316306
18. Birsoy K., Wang T., Chen W.W. An essential role of the mitochondrial electron transport chain in cell proliferation is to enable aspartate synthesis. Cell. 2015. V. 162. № 3. P. 540–551. DOI: 10.1016/j.cell.2015.07.016
19. Lewis T.L. Jr., Kwon S.-K., Lee A. et al. MFF-dependent mitochondrial fission regulates presynaptic release and axon branching by limiting axonal mitochondria size. Nat. Commun. 2018. V. 9. № 1. P. 1-17. DOI: 10.1038/s41467-018-07416-2
20. Watanabe A., Maeda K., Nara A. et al. Quantitative analysis of mitochondrial calcium uniporter (MCU) and essential MCU regulator (EMRE) in mitochondria from mouse tissues and HeLa cells. FEBS Open Bio. 2022. V. 12. № 4. P. 811–826. DOI: 10.1002/2211-5463.13371
21. Szabo I., Zoratti M. Mitochondrial channels: ion fluxes and more. Physiol. Rev. 2014. V. 94. № 2. P. 519–608. DOI: 10.1152/physrev. 00021.2013
22. Israpilova A.I., Osmanova P.M., Gadzhieva A.K., Magomedova K.M. Sovremennye predstavleniya o roli mitokhondriy v funktsionirovanii kletki. Mezhdunarodnyy studencheskiy vestnik. 2020. № 5. P. 13-18. (in Russian).
23. Lychkovskaya E.V., Trufanova L.V., Belova O.A. i dr. Rol' mitokhondriy v regulyatsii kal'tsievoy signalizatsii limfotsitov. Sibirskoe meditsinskoe obozrenie. 2016. № 5 (101). P. 5–14. (in Russian).
24. Frantsiyants E.M., Neskubina I.V., Sheyko E.A. Mitokhondrii transformirovannoy kletki kak mishen' protivoopukholevogo vozdeystviya. Issledovaniya i praktika v meditsine. 2020. V. 7. № 2. P. 92–108. DOI: 10.17709/2409-2231-2020-7-2-9 (in Russian).
25. Kit O.I., Frantsiyants E.M., Neskubina I.V. i dr. Vliyanie varianta razvitiya melanomy V16/F10 na soderzhanie Vcl-2 v mitokhondriyakh kletok razlichnykh organov samok myshey. Byulleten' sibirskoy meditsiny. 2021. T. 8. № 1. S. 46–53. DOI: 10.20538/1682-0363-2021-3-46-53 (in Russian).
26. Aouacheria A., Baghdiguian S., Lamb H.M. et al. Connecting mitochondrial dynamics and life-or-death events via Bcl-2 family proteins. Neurochem. Int. 2017. V. 109. P. 141-161. DOI: 10.1016/j.neuint.2017.04.009
27. Bock F.J., Tait S.W.G. Mitochondria as multifaceted regulators of cell death. Nat. Rev. Mol. Cell. Biol. 2020. V. 21. № 2. P. 85–100. DOI: 10.1038/s41580-019-0173-8
28. Stiban J., So M., Kaguni L.S. Iron-Sulfur Clusters in Mitochondrial Metabolism: Multifaceted Roles of a Simple Cofactor. Biochemistry (Moscow). 2016. V. 81. № 10. P. 1066–1080. DOI: 10.1134/S0006297916100059
29. Uspenskaya Yu.A., Malinovskaya N.A., Salmina A.B. Mezhkletochnyy transport mitokhondriy: molekulyarnye mekhanizmy i rol' v podderzhanii energeticheskogo gomeostaza v tkanyakh. Tsitologiya. 2021. T. 63. № 6. S. 513–530. DOI: 10.31857/S0041377121060110 (in Russian).
30. Kit O.I., Frantsiyants E.M., Shikhlyarova A.I., Neskubina I.V. Mekhanizmy estestvennogo perenosa mitokhondriy v norme i pri onkopatologii. Ul'yanovskiy mediko-biologicheskiy zhurnal. 2023. № 3. S. 14–29. DOI: 10.34014/2227-1848-2023-3-14-29 (in Russian).
31. Kazakov V.M., Skoromets A.A., Rudenko D.I. i dr. Mitokhondrial'nye bolezni: miopatii, entsefalomiopatii i entsefalomielopolinevropatii. Nevrologicheskiy zhurnal. 2018. № 6. S. 272–280. DOI: 10.18821/1560-9545-2018-23-6-272-281 (in Russian).
32. Rushkevich Yu.N., Mal'gina E.V., Badamshin R.R. i dr. Nasledstvennye miopatii u vzroslykh. Meditsinskie novosti. 2021. № 2 (317). S. 23–28. (in Russian).
33. Puzakov K.K. Aktual'nost' issledovaniy mitokhondrial'nykh tsitopatiy dlya meditsiny. Byulleten' meditsinskikh internet-konferentsiy. 2017. T. 7. № 6. S. 1082. (in Russian).
34. Gerbitz K.D., Van Den Ouweland J.M., Maassen J.A., Jaksch M. Mitochondrial diabetes mellitus: a review. Biochim. Biophys. Acta (BBA) Mol. Basis Dis. 1995. V. 1271. № 1. P. 253–260. DOI: 10.1016/0925-4439(95)00036-4
35. Polekhina N.V., Fedotova E.Yu., Baydina E.V. i dr. Nasledstvennaya opticheskaya nevropatiya Lebera: obzor literatury i klinicheskoe nablyudenie. Nervnye bolezni. 2018. № 3. S. 63–68. (in Russian).
36. Joshi A.U., Mochly-Rosen D. Mortal engines: Mitochondrial bioenergetics and dysfunction in neurodegenerative diseases. Pharmacol. Res. 2018. V. 138. P. 2–15. DOI: 10.1016/j.phrs.2018.08.010
37. Kurbatov S.A., Fedotov V.P., Tsygankova P.G. i dr. Differentsial'naya diagnostika mitokhondrial'noy neyrogastrointestinal'noy entsefalomiopatii. Pervoe klinicheskoe opisanie v Rossii. Nervno-myshechnye bolezni. 2015. T. 5. № 2. S. 44–54. DOI: 10.17650/2222-8721-2015-5-2-44-54 (in Russian).
38. Saprunova V.B., Bakeeva L.E., Yaguzhinskiy L.S. Ul'trastruktura mitokhondriy kardiomiotsitov v usloviyakh anoksii na modeli perezhivayushchey tkani serdtsa. Mitokhondrii v patologii. Pushchino. 2001. S. 71–74. (in Russian).
39. Andreev A.Yu., Kushnareva E.Yu., Starkov A.A. Metabolizm aktivnykh form kisloroda v mitokhondriyakh. Biokhimiya. 2005. V. 70. № 2. P. 246–264. (in Russian).
40. Allemailem S.K., Almatroudi A., Alsahli M.A. et al. Novel Strategies for Disrupting Cancer-Cell Functions with Mitochondria-Targeted Antitumor Drug-Loaded Nanoformulations. Int. J. Nanomedicine. 2021. V. 16. P. 3907–3936. DOI: 10.2147/IJN.S303832
41. Hsu C.C., Tseng L.M., Lee H.C. Role of mitochondrial dysfunction in cancer progression. Exp. Biol. Med. (Maywood, N.J.). 2016. V. 241. № 12. P. 1281–1295. DOI: 10.1177/1535370216641787
42. Grasso D., Zampieri L.X., Capelôa T. et al. Mitochondria in cancer. Cell Stress. 2020. V. 4. № 6. P. 114–146. DOI: 10.15698/cst2020.06.221
43. Seyfried T.N. Cancer as a mitochondrial metabolic disease. Front. Cell Dev. Biol. 2015. V. 3. P. 43. DOI: 10.3389/fcell.2015.00043
44. Trotta A.P., Chipuk J.E. Mitochondrial dynamics as regulators of cancer biology. Cell. Mol. Life Sci. 2017. V. 74. № 11. P. 1999–2017. DOI: 10.1007/s00018-016-2451-3
45. Deev R.V., Bilyalov A.I., Zhampeisov T.M. Sovremennye predstavleniya o kletochnoy gibeli. Geny i kletki. 2018. T. 13. № 1. S. 6–19. DOI: 10.23868/201805001 (in Russian).
46. Boroughs L.K., DeBerardinis R.J. Metabolic pathways promoting cancer cell survival and growth. Nat. Cell. Biol. 2015. V. 17. № 4. P. 351–359. DOI: 10.1038/ncb3124
47. Podlesnaya P.A., Kovalyova O.V., Malashenko O.S. i dr. Opukhole-spetsifichnye i opukhole-assotsiirovannye antigeny kak misheni dlya immunoterapii. Tekhnologii zhivykh sistem. 2024. T. 21. № 3. S. 53–66. DOI: 10.18127/j20700997-202403-06 (in Russian).
48. Zong W.Z., Rabinowitz J.D., White E. Mitochondria and Cancer. Mol. Cell. 2016. V. 61. № 5. P. 667–676. DOI: 10.1016/j.molcel.2016.02.011
49. Valdés-Aguayo J.J., Garza-Veloz I., Badillo-Almaráz J.I. et al. Mitochondria and Mitochondrial DNA: Key Elements in the Pathogenesis and Exacerbation of the Inflammatory State Caused by COVID-19. Medicina. 2021. V. 57. № 9. P. 928. DOI: 10.3390/medicina57090928