Russian Journal of Biological Physics and Chemisrty Russian Journal of Biological Physics and Chemisrty АКТУАЛЬНЫЕ ВОПРОСЫ БИОЛОГИЧЕСКОЙ ФИЗИКИ И ХИМИИ 2499-9962 54424 МЕДИЦИНСКАЯ БИОФИЗИКА И БИОФИЗИЧЕСКАЯ ХИМИЯ MEDICAL BIOPHYSICS AND BIOPHYSICAL CHEMISTRY МЕДИЦИНСКАЯ БИОФИЗИКА И БИОФИЗИЧЕСКАЯ ХИМИЯ ADAPTOGENIC PROPERTIES OF RESVERATROL АДАПТОГЕННЫЕ СВОЙСТВА РЕСВЕРАТРОЛА Жигачева И В Zhigacheva I V zhigacheva@mail.ru Крикунова Н. И. Krikunova N. I. Русина И Ф Rusina I F rusina939@mail.ru Расулов М. М. Rasulov M. M. rasulovmaksud@gmail.com Институт биохимической физики им. Н.М. Эмануэля РАН ru N.M. Emanuel Institute of Biochemical Physics, Russian Academy of Sciences ru Институт биохимической физики им. Н.М. Эмануэля РАН Москва Россия N.M. Emanuel Institute of Biochemical Physics, Russian Academy of Sciences Moscow Russian Federation Институт химической физики им. Н.Н. Семенова РАН ru N.N. Semenov Institute of Chemical Physics Russian Academy of Sciences ru Государственный научно-исследовательский институт химии и технологии элементоорганических соединений Москва Россия State Scientific Research Institute of Chemistry and Technology of Organoelement Compounds Moscow Russian Federation 25 06 2019 25 06 2019 4 2 226 232 20 06 2019 20 06 2019 https://rusjbpc.ru/en/nauka/article/54424/view

Исследована биологическая и антирадикальная активность природного полифенола - ресвератрола. (РВ). Хемилюминесцентным методом показаны высокие значения антирадикальной активности этого препарата. При этом на модельной системе «старения» митохондрий (инкубация митохондрий в гипотонической инкубационной среде) продемонстрировано, что препарат в диапазоне концентраций 10-5 - 10-14М предотвращал активацию ПОЛ в мембранах митохондрий печени крыс и митохондрий проростков гороха, что, вероятно, свидетельствовало о наличии у РВ антистрессовых свойств. Протекторные свойства препарата исследовали, используя модель острой гипобарической гипоксии (ОГГ) для крыс и модель дефицита воды для проростков гороха. ОГГ приводила к 1,5-3-кратному росту интенсивности флуоресценции продуктов ПОЛ в мембранах митохондрий. Активация ПОЛ сопровождалась изменениями в жирнокислотном (ЖК) составе общей липидной фракции мембран митохондрий. Коэффициент ненасыщенности С18 ЖК снижался на 15%, а содержание ЖК с очень длинной цепью (ЖКОДЦ): 22:4ω6 и 22:5ω3 снижалось почти на 28%. Введение животным 2,2×10-5М ресвератрола в течение 5 дней предотвращало изменения жирнокислотного состава митохондрий и активацию ПОЛ, что влияло на физиологические показатели. Ресвератрол в 2,0-2,5 раза увеличивал продолжительность жизни и на 10-15% повышал выживаемость мышей при различных видах гипоксии. Кроме того, препарат предотвращал торможение роста проростков гороха в условиях дефицита воды. Делается предположение, что адаптогенные свойства препарата обусловлены его антиоксидантной и антирадикальной активностью.

The biological and anti-radical activity of natural polyphenol - resveratrol (RV) was investigated. Chemiluminescent method showed high rates of antiradical activity of this drug. At the same time, on the model system of “aging” of mitochondria (incubation of mitochondria in the hypotonic incubation medium), it was shown that the drug in the concentration range of 10-5-10-14 M prevented the activation of LPO in the mitochondrial membranes of the rat liver and mitochondria of pea seedlings, which probably testified to the presence of anti-stress properties in RV. The protective properties of the drug were investigated using a model of acute hypobaric hypoxia (AHH) for rats and a model of water deficiency for pea seedlings. AHH resulted in a 1.5-3-fold increase in the fluorescence intensity of LPO products in mitochondrial membranes. The activation of lipid peroxidation was accompanied by changes in the fatty acid (FA) composition of the total lipid fraction of mitochondrial membranes. The unsaturation coefficient of C18 FA decreased by 15%, and the content of FA with a very long chain (VLCFAs): 22: 4ω6 and 22: 5ω3 decreased by almost 28%.Introduction of 2.2×10-5M resveratrol to animals within 5 days prevented changes in fatty acid composition of mitochondria and activation of LPO, which influenced physiological parameters. Resveratrol 2.0-2.5 times increased life expectancy and 10-15% increased the survival of mice in various types of hypoxia. In addition, the drug prevented inhibition of growth of pea seedlings in conditions of water scarcity. It is suggested that the adaptogenic properties of the drug are due to its antioxidant and antiradical activity.

 ресвератрол ПОЛ митохондрии жирнокислотный состав мембран острая гипобарическая гипоксия дефицит воды resveratrol POL mitochondria fatty acid composition of membranes acute hypobaric hypoxia water deficiency

Diaz-Gerevini G.T., Repossi G., Dain A., Tarres M.C., Das U.N., Eynard A.R. Beneficial action of resveratrol: How and why? Nutrition, 2016, vol. 32, pp. 174-178. DOI: 10.1016/j.nut.2015.08.017. Diaz-Gerevini G.T., Repossi G., Dain A., Tarres M.C., Das U.N., Eynard A.R. Beneficial action of resveratrol: How and why? Nutrition, 2016, vol. 32, pp. 174-178. DOI: 10.1016/j.nut.2015.08.017. Jeandet P., Douillet-Breuil A.C., Bessis R., Debord S., Sbaghi M., Adrian M. Phytoalexins from the Vitaceae: biosynthesis, phytoalexin gene expression in transgenic plants,antifungal activity, and metabolism. Journal of Agricultural and Food Chemistry, 2002, vol. 50, no. 10, pp. 2731-2741. DOI: 10.1021/jf011429s. Jeandet P., Douillet-Breuil A.C., Bessis R., Debord S., Sbaghi M., Adrian M. Phytoalexins from the Vitaceae: biosynthesis, phytoalexin gene expression in transgenic plants,antifungal activity, and metabolism. Journal of Agricultural and Food Chemistry, 2002, vol. 50, no. 10, pp. 2731-2741. DOI: 10.1021/jf011429s. Cucciolla V., Borriello A., Oliva A., Galletti P., Zappia V., Ragione F.D. Resveratrol: From basic science to the clinic. Cell Cycle, 2007, vol. 6, no. 20, pp. 2495-2510. DOI: 10.4161/cc.6.20.4815. Cucciolla V., Borriello A., Oliva A., Galletti P., Zappia V., Ragione F.D. Resveratrol: From basic science to the clinic. Cell Cycle, 2007, vol. 6, no. 20, pp. 2495-2510. DOI: 10.4161/cc.6.20.4815. Shigematsu S., Ishida S., Hara M., Takahashi N., Yoshimatsu H., Sakata T. et al. Resveratrol, a red wine constituent polyphenol, prevents superoxide-dependent inflammatory responses induced by ischemia/reperfusion, platelet-activating factor, or oxidants. Free Radic Biol Med., 2003, vol. 34, pp. 810-817. pmid: 1265446. Shigematsu S., Ishida S., Hara M., Takahashi N., Yoshimatsu H., Sakata T. et al. Resveratrol, a red wine constituent polyphenol, prevents superoxide-dependent inflammatory responses induced by ischemia/reperfusion, platelet-activating factor, or oxidants. Free Radic Biol Med., 2003, vol. 34, pp. 810-817. pmid: 1265446. Baur J.A., Sinclair D.A. Therapeutic potential of resveratrol: the in vivo evidence. Nature Reviews Drug Discovery, 2006, vol. 5, pp. 493-506. Baur J.A., Sinclair D.A. Therapeutic potential of resveratrol: the in vivo evidence. Nature Reviews Drug Discovery, 2006, vol. 5, pp. 493-506. Muhammad M.H., Allam M.M. Resveratrol and/or exercise training counteract aging-associated decline of physical endurance in aged mice; targeting mitochondrial biogenesis and function. J. Physiol. Sci., 2018, vol. 68, no. 5, pp. 681-688. DOI: 10.1007/s12576-017-0582-4. Muhammad M.H., Allam M.M. Resveratrol and/or exercise training counteract aging-associated decline of physical endurance in aged mice; targeting mitochondrial biogenesis and function. J. Physiol. Sci., 2018, vol. 68, no. 5, pp. 681-688. DOI: 10.1007/s12576-017-0582-4. Saiko P., Szakmary A., Jaeger W., Szekeres T. Resveratrol and its analogs: defense against cancer, coronary disease and neurodegenerative maladies or just a fad? Mutat. Res., 2008, vol. 658, no. 1-2, pp. 68-94. DOI: 10.1016/j.mrrev.2007.08.004 Saiko P., Szakmary A., Jaeger W., Szekeres T. Resveratrol and its analogs: defense against cancer, coronary disease and neurodegenerative maladies or just a fad? Mutat. Res., 2008, vol. 658, no. 1-2, pp. 68-94. DOI: 10.1016/j.mrrev.2007.08.004 LaFoya B., Munroe J.A., Albig A.R. A comparison of resveratrol and other polyphenolic compounds on Notch activation and endothelial cell activity. PLoS/ One, 2019, vol. 14, no. 1, p. e0210607. DOI: 10.1371/journal.pone.0210607. LaFoya B., Munroe J.A., Albig A.R. A comparison of resveratrol and other polyphenolic compounds on Notch activation and endothelial cell activity. PLoS/ One, 2019, vol. 14, no. 1, p. e0210607. DOI: 10.1371/journal.pone.0210607. Дергилев К.В., Зубкова Е.С., Белоглазова И.Б., Меньшиков М.Ю., Парфенова Е.В. Сигнальный путь Notch - терапевтическая мишень для регуляции репаративных процессов в сердце. Терапевтический архив, 2018, № 12, с. 112-121. [Dergilev K.V., Zubkova E.S., Beloglazova I.B., Menshikov M.Yu., Parfenova E.V. Notch signaling pathway is a therapeutic target for the regulation of reparative processes in the heart. Terapevticheskiy arkhiv, 2018, no. 12, pp. 112-121. (In Russ.)] Dergilev K.V., Zubkova E.S., Beloglazova I.B., Men'shikov M.Yu., Parfenova E.V. Signal'nyy put' Notch - terapevticheskaya mishen' dlya regulyacii reparativnyh processov v serdce. Terapevticheskiy arhiv, 2018, № 12, s. 112-121. [Dergilev K.V., Zubkova E.S., Beloglazova I.B., Menshikov M.Yu., Parfenova E.V. Notch signaling pathway is a therapeutic target for the regulation of reparative processes in the heart. Terapevticheskiy arkhiv, 2018, no. 12, pp. 112-121. (In Russ.)] Gueguen N., Desquiret-Dumas V., Leman G., Chupin St., Baron St., Nivet-Antoine V., Vessières E., Ayer A., Henrion D., Lenaers G., Reynier P., Procaccio V. Resveratrol Directly Binds to Mitochondrial Complex I and Increases Oxidative Stress in Brain Mitochondria of Aged Mice Increases. Oxidative Stress in Brain Mitochondria of Aged Mice. Plose/One, 2015, vol. 10, no.12, p. e0144290. Gueguen N., Desquiret-Dumas V., Leman G., Chupin St., Baron St., Nivet-Antoine V., Vessières E., Ayer A., Henrion D., Lenaers G., Reynier P., Procaccio V. Resveratrol Directly Binds to Mitochondrial Complex I and Increases Oxidative Stress in Brain Mitochondria of Aged Mice Increases. Oxidative Stress in Brain Mitochondria of Aged Mice. Plose/One, 2015, vol. 10, no.12, p. e0144290. Moreira A.C., Silva A.M., Santos M.S., Sardão V. A Resveratrol affects differently rat liver and brain mitochondrial bioenergetics and oxidative stress in vitro: Investigation of the role of gender. Food and Chemical Toxicology, 2013, vol. 53, pp. 18-26. DOI: 10.1016/j.fct.2012.11.031. Moreira A.C., Silva A.M., Santos M.S., Sardão V. A Resveratrol affects differently rat liver and brain mitochondrial bioenergetics and oxidative stress in vitro: Investigation of the role of gender. Food and Chemical Toxicology, 2013, vol. 53, pp. 18-26. DOI: 10.1016/j.fct.2012.11.031. Gadacha W., Ben-Attia M., Bonnefont-Rousselot D., Aouani E., Ghanem-Boughanmi N., Touitou Y. Resveratrol opposite effects on rat tissue lipoperoxidation: pro-oxidant during day-time and antioxidant at night. Redox Rep., 2009, vol. 14, no. 4, pp. 154-158. DOI: 10.1179/135100009X466131. Gadacha W., Ben-Attia M., Bonnefont-Rousselot D., Aouani E., Ghanem-Boughanmi N., Touitou Y. Resveratrol opposite effects on rat tissue lipoperoxidation: pro-oxidant during day-time and antioxidant at night. Redox Rep., 2009, vol. 14, no. 4, pp. 154-158. DOI: 10.1179/135100009X466131. European Convention for the Protection of Vertebrate Animals Used for Experimental and other Scientific Purposes (ETS 123), Strasburg, 1986 European Convention for the Protection of Vertebrate Animals Used for Experimental and other Scientific Purposes (ETS 123), Strasburg, 1986 Каркищенко Н.Н., Грачевой С.В. Руководство по лабораторным животным и альтернативным моделям в биомедицинских исследованиях. М: Профиль, 2010, 358 с. [Karkishchenko N.N., Gracheva S.V. Manual on laboratory animals and alternative models in biomedical research. M: Profil’, 2010, 358 p. (In Russ.)] Karkischenko N.N., Grachevoy S.V. Rukovodstvo po laboratornym zhivotnym i al'ternativnym modelyam v biomedicinskih issledovaniyah. M: Profil', 2010, 358 s. [Karkishchenko N.N., Gracheva S.V. Manual on laboratory animals and alternative models in biomedical research. M: Profil’, 2010, 358 p. (In Russ.)] Mokhova E.N., Skulachev V.P., Zhigacheva I.V. Activation of external pathway of NADH oxidation in liver mitochondria of cold-adapted rats. BBA, 1978, vol. 501, no. 3, pp. 415-423. DOI: 10.1016/0005-2728(78)90109-3. Mokhova E.N., Skulachev V.P., Zhigacheva I.V. Activation of external pathway of NADH oxidation in liver mitochondria of cold-adapted rats. BBA, 1978, vol. 501, no. 3, pp. 415-423. DOI: 10.1016/0005-2728(78)90109-3. Попов В.Н., Руге Э.К., Старков А.А. Влияние ингибиторов электронного транспорта на образование активных форм кислорода при окислении сукцината митохондриями гороха. Биохимия, 2003, т. 686, № 7, с. 910-916 [Popov V.N., Ruge E.K., Starkov A.A. The effect of electron transport inhibitors on the formation of reactive oxygen species during the oxidation of succinate with pea mitochondria. Biokhimiya, 2003, vol. 686, no 7, pp. 910-916. DOI: 10.1023/A:1025078815819. (In Russ)] Popov V.N., Ruge E.K., Starkov A.A. Vliyanie ingibitorov elektronnogo transporta na obrazovanie aktivnyh form kisloroda pri okislenii sukcinata mitohondriyami goroha. Biohimiya, 2003, t. 686, № 7, s. 910-916 [Popov V.N., Ruge E.K., Starkov A.A. The effect of electron transport inhibitors on the formation of reactive oxygen species during the oxidation of succinate with pea mitochondria. Biokhimiya, 2003, vol. 686, no 7, pp. 910-916. DOI: 10.1023/A:1025078815819. (In Russ)] Fletcher B.I., Dillard C.D., Tappel A.L. Measurement of Fluorescent Lipid Peroxidation Products in Biological Systems and Tissues. Ann. Biochem., 1973, vol. 52, no. 1, p. 1-9. DOI: 10.1016/0003-2697(73)90327-8. Fletcher B.I., Dillard C.D., Tappel A.L. Measurement of Fluorescent Lipid Peroxidation Products in Biological Systems and Tissues. Ann. Biochem., 1973, vol. 52, no. 1, p. 1-9. DOI: 10.1016/0003-2697(73)90327-8. Шляпинтох В.Я., Карпухин О.Н., Постников Л.М., Захаров И.В., Вичутинский А.А., Цепалов В.Ф. Хемилюминесцентные методы исследования медленных химических процессов. М: Наука, 1966, 300 с. [Shlyapintokh V.Ya., Karpukhin O.N., Postnikov L.M., Zakharov I.V., Vichutinsky A.A., Tsepalov V.F. Chemiluminescent methods for the investigation of slow chemical processes. M: Nauka. 1966, 300 p. (In Russ.)] Shlyapintoh V.Ya., Karpuhin O.N., Postnikov L.M., Zaharov I.V., Vichutinskiy A.A., Cepalov V.F. Hemilyuminescentnye metody issledovaniya medlennyh himicheskih processov. M: Nauka, 1966, 300 s. [Shlyapintokh V.Ya., Karpukhin O.N., Postnikov L.M., Zakharov I.V., Vichutinsky A.A., Tsepalov V.F. Chemiluminescent methods for the investigation of slow chemical processes. M: Nauka. 1966, 300 p. (In Russ.)] Carreau J.P., Dubacq J.P. Adaptation of Macroscale Method to the Microscale for Fatty Acid Methyl Transesterification of Biological Lipid Extracts. J. Chromatogr., 1979, vol. 151, no. 3, pp. 384-390. DOI: 10.1016/S0021-9673(00)88356-9Get. Carreau J.P., Dubacq J.P. Adaptation of Macroscale Method to the Microscale for Fatty Acid Methyl Transesterification of Biological Lipid Extracts. J. Chromatogr., 1979, vol. 151, no. 3, pp. 384-390. DOI: 10.1016/S0021-9673(00)88356-9Get. Wang J., Sunwoo H., Cherian G., Sim I.S. Fatty Acid Determination in Chicken Egg Yolk: a Comparison of Different Methods Poultry. Sci., 2000, vol. 79, no. 8, pp. 1168-1171. DOI: 10.1093/ps/79.8.1168. Wang J., Sunwoo H., Cherian G., Sim I.S. Fatty Acid Determination in Chicken Egg Yolk: a Comparison of Different Methods Poultry. Sci., 2000, vol. 79, no. 8, pp. 1168-1171. DOI: 10.1093/ps/79.8.1168. Golovina R.V., Kuzmenko T.E. Thermodynamic Evaluation Interaction of Fatty Acid Methyl Esters with Polar and Nonpolar Stationary Phases, Based on Their Retention Indices. Сhromatogr., 1977, vol. 10, no. 9, pp. 545-546. URL: https://link.springer.com/article/10.1007%2FBF02262915. Golovina R.V., Kuzmenko T.E. Thermodynamic Evaluation Interaction of Fatty Acid Methyl Esters with Polar and Nonpolar Stationary Phases, Based on Their Retention Indices. Shromatogr., 1977, vol. 10, no. 9, pp. 545-546. URL: https://link.springer.com/article/10.1007%2FBF02262915. Зоров Д.Б., Исаев Н.К., Плотников Е.Ю., Зорова Л.Д., Стельмашук Е.В., Васильева А.К., Архангельская А.А., Хряпенкова Е.Г. Митохондрии как многоликий янус. Биохимия, 2007, т. 72, № 10, с. 1371-1384. [Zorov D.B., Isaev N.K., Plotnikov E.Yu., Zorova L.D., Stelmashuk E.V., Vasilyeva A.K., Arkhangelskaya A.A., Khryapenkova E.G. Mitochondria as a multifaceted Janus. Biokhimiya, 2007, vol. 72, no. 10, p. 1371-1384. (In Russ.)] Zorov D.B., Isaev N.K., Plotnikov E.Yu., Zorova L.D., Stel'mashuk E.V., Vasil'eva A.K., Arhangel'skaya A.A., Hryapenkova E.G. Mitohondrii kak mnogolikiy yanus. Biohimiya, 2007, t. 72, № 10, s. 1371-1384. [Zorov D.B., Isaev N.K., Plotnikov E.Yu., Zorova L.D., Stelmashuk E.V., Vasilyeva A.K., Arkhangelskaya A.A., Khryapenkova E.G. Mitochondria as a multifaceted Janus. Biokhimiya, 2007, vol. 72, no. 10, p. 1371-1384. (In Russ.)] Aronis A., Komarnitsky R., Shilo Sh., Tirosh O. Membrane depolarization of isolated rat liver mitochondria attenuates permeability transition pore opening and oxidant production. Antioxidant and redox signaling, 2004, vol. 4, no. 4, p. 647-654. DOI: 10.1089/15230860260220157. Aronis A., Komarnitsky R., Shilo Sh., Tirosh O. Membrane depolarization of isolated rat liver mitochondria attenuates permeability transition pore opening and oxidant production. Antioxidant and redox signaling, 2004, vol. 4, no. 4, p. 647-654. DOI: 10.1089/15230860260220157. O’Rourke B. Mitochondrial Ion Channels. Annual Review of Physiol., 2007, vol. 69, pp. 19-49. DOI: 10.1146/annurev.physiol.69.031905.163804. O’Rourke B. Mitochondrial Ion Channels. Annual Review of Physiol., 2007, vol. 69, pp. 19-49. DOI: 10.1146/annurev.physiol.69.031905.163804. Генерозова И.П., Шугаев А.Г. Респираторный метаболизм митохондрий проростков гороха разного возраста в условиях дефицита воды. Физиол. растений, 2012, т. 596, № 2, с. 262-227. [Generozova I.P., Shugaev A.G. Respiratory metabolism of mitochondria of pea seedlings of different ages under conditions of water deficiency. Fiziolyu rasteniy, 2012, vol. 596, no. 2, pp. 262-227. (In Russ.)] Generozova I.P., Shugaev A.G. Respiratornyy metabolizm mitohondriy prorostkov goroha raznogo vozrasta v usloviyah deficita vody. Fiziol. rasteniy, 2012, t. 596, № 2, s. 262-227. [Generozova I.P., Shugaev A.G. Respiratory metabolism of mitochondria of pea seedlings of different ages under conditions of water deficiency. Fiziolyu rasteniy, 2012, vol. 596, no. 2, pp. 262-227. (In Russ.)] Koster K.L., Reisdorph N., Ramsau J.L. Changing Desiccation Tolerance of Pea Embryo Protoplasts during Germination. J. Exp. Bot., 2003, vol. 54, pp. 1607-1614. DOI: 10.1093/jxb/erg17. Koster K.L., Reisdorph N., Ramsau J.L. Changing Desiccation Tolerance of Pea Embryo Protoplasts during Germination. J. Exp. Bot., 2003, vol. 54, pp. 1607-1614. DOI: 10.1093/jxb/erg17. Okçu G., Kaya M.D., Atak M. Effects of Salt and Drought Stresses on Germination and Seedling Growth of Pea (Pisum sativum L.). Turk. J. Agric. For., 2005, vol. 29, pp. 237-242. Okçu G., Kaya M.D., Atak M. Effects of Salt and Drought Stresses on Germination and Seedling Growth of Pea (Pisum sativum L.). Turk. J. Agric. For., 2005, vol. 29, pp. 237-242. Paradies G., Petrosillo G., Pistolese M., Venosa N., Federici A., Ruggiero F.M. Decrease in Mitochondrial Complex I Activity in Ischemic/Perfused Rat Heart. Involvement of Reactive Oxygen Species and Cardiolipin. Circulation Research., 2004, vol. 94, no. 1, pp. 53-59. DOI: 10.1161/01.RES.0000109416.56608.64. Paradies G., Petrosillo G., Pistolese M., Venosa N., Federici A., Ruggiero F.M. Decrease in Mitochondrial Complex I Activity in Ischemic/Perfused Rat Heart. Involvement of Reactive Oxygen Species and Cardiolipin. Circulation Research., 2004, vol. 94, no. 1, pp. 53-59. DOI: 10.1161/01.RES.0000109416.56608.64. Acin-Perez R., Enriquez J.A. The function of the respiratory supercomplexes: The plasticity model. Biochimica et Biophysica Acta, 2014, vol. 1837, no. 4, pp. 444-450. DOI: 10.1016/j.bbabio.2013.12.009. Acin-Perez R., Enriquez J.A. The function of the respiratory supercomplexes: The plasticity model. Biochimica et Biophysica Acta, 2014, vol. 1837, no. 4, pp. 444-450. DOI: 10.1016/j.bbabio.2013.12.009. de Carvalho C.C.C.R., Caramujo M.J. The Various Roles of Fatty Acids. Molecules, 2018, vol. 23, no. 10, pp. E 2583. DOI: 10.3390/molecules23102583. de Carvalho C.C.C.R., Caramujo M.J. The Various Roles of Fatty Acids. Molecules, 2018, vol. 23, no. 10, pp. E 2583. DOI: 10.3390/molecules23102583. Genova M.L., Lenaz G. Functional role of mitochondrial respiratory supercomplexes. Biochimica et Biophysica Acta, 2014, vol. 1837, no. 4, pp. 427-443. DOI: 10.1016/j.bbabio.2013.11.002. Genova M.L., Lenaz G. Functional role of mitochondrial respiratory supercomplexes. Biochimica et Biophysica Acta, 2014, vol. 1837, no. 4, pp. 427-443. DOI: 10.1016/j.bbabio.2013.11.002. Muller-Navarra D.C., Brett M.T., Park S., Chandra S., Ballantyne A.P., Zorita E., Goldman Ch.R. Unsaturated fatty acid content in seston and tropho-dynamic coupling in lakes. Nature, 2004, vol. 427, no. 6969, pp. 69-72. DOI: 10.1038/nature02210. Muller-Navarra D.C., Brett M.T., Park S., Chandra S., Ballantyne A.P., Zorita E., Goldman Ch.R. Unsaturated fatty acid content in seston and tropho-dynamic coupling in lakes. Nature, 2004, vol. 427, no. 6969, pp. 69-72. DOI: 10.1038/nature02210.