БИОХИМИЯ, 2019, том 84, вып. 12, с. 1815–1831

УДК 595.7:577.24

Биологическое разнообразие кардиолипина и его ремоделирование при окислительном стрессе и возрастных патологиях

Обзор

© 2019 Г.А. Шиловский 1,2,3*, Т.С. Путятина 2, В.В. Ашапкин 1, О.В. Ямскова 4, В.А. Любецкий 3, Е.В. Сорокина 2, С.И. Шрам 5, А.В. Марков 2, М.Ю. Высоких 1

НИИ физико-химической биологии им. А.Н. Белозерского, Московский государственный университет им. М.В. Ломоносова, 119991 Москва, Россия; электронная почта: gregory_sh@list.ru, grgerontol@gmail.com

Московский государственный университет им. М.В. Ломоносова, биологический факультет, 119234 Москва, Россия

Институт проблем передачи информации РАН, 127051 Москва, Россия

Институт элементоорганических соединений им. А.Н.Несмеянова РАН, 119991 Москва, Россия

Институт молекулярной генетики РАН, 123182 Москва, Россия

Поступила в редакцию 13.08.2019
После доработки 20.09.2019
Принята к публикации 20.09.2019

DOI: 10.1134/S0320972519120066

КЛЮЧЕВЫЕ СЛОВА: активные формы кислорода, кардиолипин, тафацин, митохондриально-направленные антиоксиданты, перекисное окисление липидов, старение.

Аннотация

Возрастная дисфункция сопровождается нарушением морфологии, сигнальных путей и белковых взаимодействий в митохондриях. Кардиолипин — один из основных фосфолипидов митохондрий, который поддерживает кривизну крист и способствует сборке и взаимодействию комплексов и суперкомплексов дыхательной цепи митохондрий. Жирнокислотный состав кардиолипина влияет на биофизические свойства мембраны и имеет решающее значение для биоэнергетики митохондрий. Наличие в составе кардиолипина жирных кислот с двойными связями опосредует его уязвимость к окислительному повреждению. Поврежденный кардиолипин подвергается ремоделированию с помощью фосфолипаз, ацилтрансфераз и трансацилаз, формирующих высокоспецифичный для ткани ацильный профиль. В обзоре рассматриваются изменения в жирнокислотном составе кардиолипина разных тканей для различных биологических видов в норме и при различных патологиях (возрастные заболевания, окислительный и травматический стрессы, а также нокауты/нокдауны ферментов пути синтеза кардиолипина). Прогрессирующие патологии, в том числе возрастного характера, сопровождаются истощением кардиолипина и снижением эффективности его ремоделирования, а также активацией альтернативного пути «патологического ремоделирования», вызывающего замену жирных кислот кардиолипина на полиненасыщенные, такие как арахидоновая или докозагексаеновая кислоты. Использование лекарственных препаратов или специальная диета могут способствовать частичному восстановлению ацильного профиля кардиолипина до формы, богатой жирными кислотами, характерными для неповрежденного органа или ткани, скорректировав последствия недостаточного ремоделирования кардиолипина при патологии. В связи с этим, актуальной задачей биомедицины является изучение механизма действия митохондриально-направленных антиоксидантов, эффективных для лечения возрастных патологий и способных накапливаться не только in vitro, но и in vivo в участках мембран, обогащенных кардиолипином.

Сноски

* Адресат для корреспонденции.

Финансирование

Исследование выполнено при финансовой поддержке РФФИ (проект 18-29-13037).

Конфликт интересов

Авторы заявляют об отсутствии конфликта интересов.

Соблюдение этических норм

В данной работе не было никаких исследований, в которых были использованы в качестве объектов люди или животные.

Список литературы

1. Feniouk, B.A., and Skulachev, V.P. (2017) Cellular and molecular mechanisms of action of mitochondria-targeted antioxidants, Curr. Aging. Sci., 10, 41–48, doi: 10.2174/1874609809666160921113706.

2. Skulachev, V.P., Anisimov, V.N., Antonenko, Y.N., Bakeeva, L.E., Chernyak, B.V., Erichev, V.P., Filenko, O.F., Kalinina, N.I., Kapelko, V.I., Kolosova, N.G., Kopnin, B.P., Korshunova, G.A., Lichinitser, M.R., Obukhova, L.A., Pasyukova, E.G., Pisarenko, O.I., Roginsky, V.A., Ruuge, E.K., Senin, I.I., Severina, I.I., Skulachev, M.V., Spivak, I.M., Tashlitsky, V.N., Tkachuk, V.A., Vyssokikh, M.Y., Yaguzhinsky, L.S., and Zorov, D.B. (2009) An attempt to prevent senescence: a mitochondrial approach, Biochim. Biophys. Acta, 1787, 437–461, doi: 10.1016/j.bbabio.2008.12.008.

3. Ames, B.N., Shigenaga, M.K., and Hagen, T.M. (1995) Mitochondrial decay in aging, Biochim. Biophys. Acta, 1271, 165–170, doi: 10.1016/0925-4439(95)00024-x.

4. Kagan, V.E., Chu, C.T., Tyurina, Y.Y., Cheikhi, A., and Bayir, H. (2014) Cardiolipin asymmetry, oxidation and signaling, Chem. Phys. Lipids, 179, 64–69, doi: 10.1016/j.chemphyslip.2013.11.010.

5. Kagan, V.E., Tyurina, Y.Y., Tyurin, V.A., Mohammadyani, D., Angeli, J.P., Baranov, S.V., Klein-Seetharaman, J., Friedlander, R.M., Mallampalli, R.K., Conrad, M., and Bayir, H. (2015) Cardiolipin signaling mechanisms: collapse of asymmetry and oxidation, Antioxid. Redox Signal., 22, 1667–1680, doi: 10.1089/ars.2014.6219.

6. Von Zglinicki, T. (1987) A mitochondrial membrane hypothesis of aging, J. Theor. Biol., 127, 127–132, doi: 10.1016/S0022-5193(87)80123-6.

7. Ye, C., Shen, Z., and Greenberg, M.L. (2016) Cardiolipin remodeling: a regulatory hub for modulating cardiolipin metabolism and function, J. Bioenerg. Biomembr., 48, 113–123, doi: 10.1007/s10863-014-9591-7.

8. Laganiere, S. and Yu, B.P. (1993) Modulation of membrane phospholipid fatty acid composition by age and food restriction, Gerontology, 39, 7–18, doi: 10.1159/000213509.

9. Tyurina, Y.Y., Tyurin, V.A., Epperly, M.W. Greenberger, J.S., and Kagan, V.E. (2008) Oxidative lipidomics of gamma-irradiation-induced intestinal injury, Free Radic. Biol. Med., 44, 299–314, doi: 10.1016/j.freeradbiomed.2007.08.021.

10. Tyurina, Y.Y., Tyurin, V.A., Kapralova, V.I., Amoscato, A.A., Epperly, M.W., Greenberger, J.S., and Kagan, V.E. (2009) Mass-spectrometric characterization of phospholipids and their hydroperoxide derivatives in vivo: effects of total body irradiation, Methods Mol. Biol., 580, 153–183, doi: 10.1007/978-1-60761-325-1_9.

11. Tyurina, Y.Y., Tyurin, V.A., Kaynar, A.M., Kapralova, V.I., Wasserloos, K., Li, J., Mosher, M., Wright, L., Wipf, P., Watkins, S., Pitt, B.R., and Kagan, V.E. (2010) Oxidative lipidomics of hyperoxic acute lung injury: mass spectrometric characterization of cardiolipin and phosphatidylserine peroxidation, Am. J. Physiol. Lung Cell. Mol. Physiol., 299, 73–85, doi: 10.1152/ajplung.00035.2010.

12. Mileykovskaya, E., Zhang, M., and Dowhan, W. (2005) Cardiolipin in energy transducing membranes, Biochemistry (Moscow), 70, 154–158, doi: 10.1007/s10541-005-0095-2.

13. Schlame, M. (2008) Cardiolipin synthesis for the assembly of bacterial and mitochondrial membranes, J. Lipid Res., 49, 1607–1620, doi: 10.1194/jlr.R700018-JLR200.

14. Corcelli, A. (2009) The cardiolipin analogues of Archaea, Biochim. Biophys. Acta, 1788, 2101–2106, doi: 10.1016/j.bbamem.2009.05.010.

15. Xu, Y., Sutachan, J.J., Plesken, H., Kelley, R.I., and Schlame, M. (2005) Characterization of lymphoblast mitochondria from patients with Barth syndrome, Lab. Invest., 85, 823–830, doi: 10.1038/labinvest.3700274.

16. Acehan, D., Khuchua, Z., Houtkooper, R.H., Malhotra, A., Kaufman, J., Vaz, F.M., Ren, M., Rockman, H.A., Stokes, D.L., and Schlame, M. (2009) Distinct effects of tafazzin deletion in differentiated and undifferentiated mitochondria, Mitochondrion, 9, 86–95, doi: 10.1016/j.mito.2008.12.001.

17. Xu, F.Y., McBride, H., Acehan, D., Vaz, F.M., Houtkooper, R.H., Lee, R.M., and Mowat, M.A., and Hatch, G.M. (2010) The dynamics of cardiolipin synthesis post-mitochondrial fusion, Biochim. Biophys. Acta, 1798, 1577–1585, doi: 10.1016/j.bbamem.2010.04.007.

18. Claypool, S.M., Oktay, Y., Boontheung, P., Loo, J.A., and Koehler, C.M. (2008) Cardiolipin defines the interactome of the major ADP/ATP carrier protein of the mitochondrial inner membrane, J. Cell. Biol., 182, 937–950, doi: 10.1083/jcb.200801152.

19. Mileykovskaya, E., and Dowhan, W. (2014) Cardiolipin-dependent formation of mitochondrial respiratory supercomplexes, Chem. Phys. Lipids, 179, 42–48, doi: 10.1016/j.chemphyslip.2013.10.012.

20. Paradies, G., Paradies, V., Ruggiero, F.M., and Petrosillo, G. (2014) Cardiolipin and mitochondrial function in health and disease, Antioxid. Redox Signal., 20, 1925–1953, doi: 10.1089/ars.2013.5280.

21. Gebert, N., Joshi, A.S, Kutik, S., Becker, T., McKenzie, M., Guan, X.L., Mooga, V.P., Stroud, D.A., Kulkarni, G., Wenk, M.R., Rehling, P., Meisinger, C., Ryan, M.T., Wiedemann, N., Greenberg, M.L., and Pfanne, N. (2009) Mitochondrial cardiolipin involved in outer-membrane protein biogenesis: implications for Barth syndrome, Curr Biol., 19, 2133–2139, doi: 10.1016/j.cub.2009.10.074.

22. Patil, V.A., Fox, J.L., Gohil, V.M., Winge, D.R, and Greenberg, M.L. (2013) Loss of cardiolipin leads to perturbation of mitochondrial and cellular iron homeostasis, J. Biol. Chem., 288, 1696–1705, doi: 10.1074/jbc.M112.428938.

23. Joshi, A.S., Zhou, J., Gohil, V.M., Chen, S., and Greenberg, M.L. (2009) Cellular functions of cardiolipin in yeast, Biochim. Biophys. Acta, 1793, 212–218, doi: 10.1016/j.bbamcr.2008.07.024.

24. Houtkooper, R.H., and Vaz, F.M. (2008) Cardiolipin, the heart of mitochondrial metabolism, Cell. Mol. Life Sci., 65, 2493–2506, doi: 10.1007/s00018-008-8030-5.

25. Cogliati, S., Frezza, C., Soriano, M.E., Varanita, T., Quintana-Cabrera, R., Corrado, M., Cipolat, S., Costa, V., Casarin, A., Gomes, L.C., Perales-Clemente, E., Salviati, L., Fernandez-Silva, P., Enriquez, J.A., and Scorrano, L. (2013) Mitochondrial cristae shape determines respiratory chain supercomplexes assembly and respiratory efficiency, Cell, 155, 160–171, doi: 10.1016/j.cell.2013.08.032.

26. Schlame, M. (2013) Cardiolipin remodeling and the function of tafazzin, Biochim. Biophys. Acta, 1831, 582–588, doi: 10.1016/j.bbalip.2012.11.007.

27. Kagan, V.E., Jiang, J., Huang, Z., Tyurina, Y.Y., Desbourdes, C., Cottet-Rousselle, C., Dar, H.H., Verma, M., Tyurin, V.A., Kapralov, A.A., Cheikhi, A., Mao, G., Stolz, D., St. Croix, C.M., Watkins, S., Shen, Z., Li, Y., Greenberg, M.L., Tokarska-Schlattner, M., Boissan, M., Lacombe, M.L., Epand, R.M., Chu, C.T., Mallampalli, R.K., Bayir, H., and Schlattner, U. (2016) NDPK-D (NM23-H4)-mediated externalization of cardiolipin enables elimination of depolarized mitochondria by mitophagy, Cell Death Differ., 23, 1140–1151, doi: 10.1038/cdd.2015.160.

28. Chu, C.T., Bayir, H., and Kagan, V.E. (2014) LC3 binds externalized cardiolipin on injured mitochondria to signal mitophagy in neurons: implications for Parkinson’s disease, Autophagy, 10, 376–378, doi: 10.4161/auto.27191.

29. Mulkidjanian, A.Y., Shalaeva, D.N., Lyamzaev, K.G., and Chernyak, B.V. (2018) Does oxidation of mitochondrial cardiolipin trigger a chain of antiapoptotic reactions? Biochemistry (Moscow), 83, 1263–1278, doi: 10.1134/S0006297918100115.

30. Petrosillo, G., Casanova, G., Matera, M., Ruggiero, F.M., and Paradies, G. (2006) Interaction of peroxidized cardiolipin with rat-heart mitochondrial membranes: induction of permeability transition and cytochrome c release, FEBS Lett., 580, 6311–6316, doi: 10.1016/j.febslet.2006.10.036.

31. Wang, Z., Ying, Z., Bosy-Westphal, A., Zhang, J., Schautz, B., Later, W., Heymsfield, S.B., and Müller, M.J. (2010) Specific metabolic rates of major organs and tissues across adulthood: evaluation by mechanistic model of resting energy expenditure, Am. J. Clin. Nutr., 92, 1369–1377, doi: 10.3945/ajcn.2010.29885.

32. Rocquelin, G., Guenot, L., Astorg, P.O., and David, M. (1989) Phospholipid content and fatty acid composition of human heart, Lipids, 24, 775–780, doi: 10.1007/bf02544583.

33. Ristic, V., Tepsic, V., De Luka, S.R., and Vrbaski, S.R. (1998) Phospholipid content and fatty acid composition in the rat heart after chronic diazepam treatment, Physiol. Res., 47, 115–118.

34. Tepsic, V., Ristic, V., Ristic, D., Vasiljevic, N., and Pecelj-Gec, M. (1998) Heart phospholipid content and fatty acid composition in the rat after feeding different lipid supplemented diets, Physiol. Res., 47, 413–418.

35. Schlame, M., Ren, M., Xu, Y., Greenberg, M.L., and Haller, I. (2005) Molecular symmetry in mitochondrial cardiolipins, Chem. Phys. Lipids, 138, 38–49, doi: 10.1016/j.chemphyslip.2005.08.002.

36. Claypool, S.M., and Koehler, C.M. (2012) The complexity of cardiolipin in health and disease, Trends Biochem. Sci., 37, 32–41, doi: 10.1016/j.tibs.2011.09.003.

37. Saric, A., Andreau, K., Armand, A.S., Møller, I.M., and Petit, P.X. (2016) Barth syndrome: from mitochondrial dysfunctions associated with aberrant production of reactive oxygen species to pluripotent stem cell studies, Front. Genet., 6, 359, doi: 10.3389/fgene.2015.00359.

38. Shen, Z., Ye, C., McCain, K., and Greenberg, M.L. (2015) The role of cardiolipin in cardiovascular health, Biomed. Res. Int., 891707, doi: 10.1155/2015/891707.

39. Maguire, J.J., Tyurina, Y.Y., Mohammadyani, D., Kapralov, A.A., Anthonymuthu, T.S., Qu, F., Amoscato, A.A., Sparvero, L.J., Tyurin, V.A., Planas-Iglesias, J., He, R.R., Klein-Seetharaman, J., Bayir, H., and Kagan, V.E. (2017) Known unknowns of cardiolipin signaling: the best is yet to come, Biochim. Biophys. Acta, 1862, 8–24, doi: 10.1016/j.bbalip.2016.08.001.

40. Guan, Z.Z., Soderberg, M., Sindelar, P., and Edlund, C. (1994) Content and fatty acid composition of cardiolipin in the brain of patients with Alzheimer’s disease, Neurochem. Int., 25, 295–300, doi: 10.1016/0197-0186(94)90073-6.

41. Divakaran, P., and Venkataraman, A. (1977) Effect of dietary fats on oxidative phosphorylation and fatty acid profile of rat liver mitochondria, J. Nutr., 107, 1621–1631, doi: 10.1093/jn/107.9.1621.

42. Kraffe, E., Soudant, P., Marty, Y., Kervarec, N., and Jehan, P. (2002) Evidence of a tetradocosahexaenoic cardiolipin in some marine bivalves, Lipids, 37, 507–514, doi: 10.1007/s11745-002-0925-z.

43. Kraffe, E., Soudant, P., Marty, Y., and Kervarec, N. (2005) Docosahexaenoic acid- and eicosapentaenoic acid-enriched cardiolipin in the Manila clam Ruditapesphilippinarum, Lipids, 40, 619–625, doi: 10.1007/s11745-005-1423-z.

44. Fajardo, V.A., Mikhaeil, J.S., Leveille, C.F., Saint, C., and LeBlanc, P.J. (2017) Cardiolipin content, linoleic acid composition, and tafazzin expression in response to skeletal muscle overload and unload stimuli, Sci. Rep., 7, 2060, doi: 10.1038/s41598-017-02089-1.

45. Diagne, A., Fauvel, J., Record, M., Chap, H., and Douste-Blazy, L. (1984) Studies on ether phospholipids. II. Comparative composition of various tissues from human, rat and guinea pig, Biochim. Biophys. Acta, 793, 221–231, doi: 10.1016/0005-2760(84)90324-2.

46. Courtade, S., Marinetti, G.V., and Stotz, E. (1967) The structure and abundance of rat tissue cardiolipins, Biochim. Biophys. Acta, 137, 121–134, doi: 10.1016/0005-2760(67)90015-x.

47. Sparagna, G.C., and Lesnefsky, E.J. (2009) Cardiolipin remodeling in the heart, J. Cardiovasc. Pharmacol., 53, 290–301, doi: 10.1097/FJC.0b013e31819b5461.

48. Lee, H., Mayette, J., Rapoport, S.I., and Bazinet, R.P. (2006) Selective remodeling of cardiolipin fatty acids in the aged rat heart, Lipids Health Dis., 5, 2, doi: 10.1186/1476-511X-5-2.

49. Schlame, M., and Otten, D. (1991) Analysis of cardiolipin molecular species by high-performance liquid chromatography of its derivative 1,3-bisphosphatidyl-2-benzoyl-sn-glycerol dimethyl ester, Anal. Biochem., 195, 290–295, doi: 10.1016/0003-2697(91)90332-n.

50. Han, X., Yang, K., Yang, J., Cheng, H., and Gross, R.W. (2006) Shotgun lipidomics of cardiolipin molecular species in lipid extracts of biological samples, J. Lipid Res., 47, 864–879, doi: 10.1194/jlr.D500044-JLR200.

51. Portero-Otin, M., Bellmunt, M.J., Ruiz, M.C., Barja, G., and Pamplona, R. (2001) Correlation of fatty acid unsaturation of the major liver mitochondrial phospholipid classes in mammals to their maximum life span potential, Lipids, 36, 491–498, doi: 10.1007/s11745-001-0748-y.

52. Wang, H.Y., Jackson, S.N., and Woods, A.S. (2007) Direct MALDI-MS analysis of cardiolipin from rat organs sections, J. Am. Soc. Mass Spectrom., 18, 567–577, doi: 10.1016/j.jasms.2006.10.023.

53. Xu, Y., Malhotra, A., Ren, M., and Schlame, M. (2006) The enzymatic function of tafazzin, J. Biol. Chem., 281, 39217–39224, doi: 10.1074/jbc.M606100200.

54. Chicco, A.J., Sparagna, G.C., McCune, S.A., Johnson, C.A., Murphy, R.C., Bolden, D.A., Rees, M.L., Gardner, R.T., and Moore, R.L. (2008) Linoleate-rich high-fat diet decreases mortality in hypertensive heart failure rats compared with lard and low-fat diets, Hypertension, 52, 549–555, doi: 10.1161/HYPERTENSIONAHA.108.114264.

55. He, Q., and Han, X. (2014) Cardiolipin remodeling in diabetic heart, Chem. Phys. Lipids, 179, 75–81, doi: 10.1016/j.chemphyslip.2013.10.007.

56. Wahjudi, P.N., Yee, J.K., Martinez, S.R., Zhang, J., Teitell, M., Nikolaenko, L., Swerdloff, R., Wang, C., and Lee, W.N. (2011) Turnover of nonessential fatty acids in cardiolipin from the rat heart, J. Lipid. Res., 52, 2226–2233, doi: 10.1194/jlr.M015966.

57. Bayir, H., Tyurin, V.A., Tyurina, Y.Y., Viner, R., Ritov, V., Amoscato, A.A., Zhao, Q., Zhang, X.J., Janesko-Feldman, K.L., Alexander, H., Basova, L.V., Clark, R.S, Kochanek, P.M., and Kagan, V.E. (2007) Selective early cardiolipin peroxidation after traumatic brain injury: an oxidative lipidomics analysis, Ann. Neurol., 62, 154–169, doi: 10.1002/ana.21168.

58. Cheng, H., Mancuso, D.J., Jiang, X., Guan, S., Yang, J., Yang, K., Sun, G., Gross, R.W., and Han, X. (2008) Shotgun lipidomics reveals the temporally dependent, highly diversified cardiolipin profile in the mammalian brain: temporally coordinated postnatal diversification of cardiolipin molecular species with neuronal remodeling, Biochemistry, 47, 5869–5880, doi: 10.1021/bi7023282.

59. Ji, J., Kline, A.E., Amoscato, A., Samhan-Arias, A.K., Sparvero, L.J., Tyurin, V.A., Tyurina, Y.Y., Fink, B., Manole, M.D., Puccio, A.M., Okonkwo, D.O., Cheng, J.P., Alexander, H., Clark, R.S., Kochanek, P.M., Wipf, P., Kagan, V.E., and Bayir, H. (2012) Lipidomics identifies cardiolipin oxidation as a mitochondrial target for redox therapy of brain injury, Nat. Neurosci., 15, 1407–1413, doi: 10.1038/nn.3195.

60. Kiebish, M.A., Han, X., Cheng, H., Chuang, J.H., and Seyfried, T.N. (2008) Cardiolipin and electron transport chain abnormalities in mouse brain tumor mitochondria: lipidomic evidence supporting the Warburg theory of cancer, J. Lipid Res., 49, 2545–2556, doi: 10.1194/jlr.M800319-JLR200.

61. Yabuuchi, H., and O’Brien, J. (1968) Brain cardiolipin: isolation and fatty acid positions, J. Neurochem., 15, 1383–1390, doi: 10.1111/j.1471-4159.1968.tb05920.x.

62. Li, J., Romestaing, C., Han, X., Li, Y., Hao, X., Wu, Y., Sun, C., Liu, X., Jefferson, L.S., Xiong, J., Lanoue, K.F., Chang, Z., Lynch, C.J., Wang, H., and Shi, Y. (2010) Cardiolipin remodeling by ALCAT1 links oxidative stress and mitochondrial dysfunction to obesity, Cell Metab., 12, 154–165, doi: 10.1016/j.cmet.2010.07.003.

63. Maddalena, L.A., Ghelfi, M., Atkinson, J., and Stuart, J.A. (2017) The mitochondria-targeted imidazole substituted oleic acid ′TPP-IOA′ affects mitochondrial bioenergetics and its protective efficacy in cells is influenced by cellular dependence on aerobic metabolism, Biochim. Biophys. Acta, 1858, 73–85, doi: 10.1016/j.bbabio.2016.11.005.

64. Daiyasu, H., Kuma, K., Yokoi, T., Morii, H., Koga, Y., and Toh, H. (2005) A study of archaeal enzymes involved in polar lipid synthesis linking amino acid sequence information, genomic contexts and lipid composition, Archaea, 1, 399–410, doi: 10.1155/2005/452563.

65. Gu, Z., Valianpou, F., Chen, S., Vaz, F.M., Hakkaart, G.A., Wanders, R.J., and Greenberg, M.L. (2004) Aberrant cardiolipin metabolism in the yeast taz1 mutant: a model for Barth syndrome, Mol. Microbiol., 51, 149–158, doi: 10.1046/j.1365-2958.2003.03802.x.

66. Cao, J., Liu, Y., Lockwood, J., Burn, P., and Shi, Y. (2004) A novel cardiolipin-remodeling pathway revealed by a gene encoding an endoplasmic reticulum-associated acyl-CoA: lysocardiolipin acyltransferase (ALCAT1) in mouse, J. Biol. Chem., 279, 31727–31734, doi: 10.1074/jbc.M402930200.

67. Ren, M., Phoon, C.K., and Schlame, M. (2014) Metabolism and function of mitochondrial cardiolipin, Prog. Lipid Res., 55, 1–16, doi: 10.1016/j.plipres.2014.04.001.

68. Sullivan, E.M., Pennington, E.R., Sparagna, G.C., Torres, M.J., Neufer, P.D., Harris, M., Washington, J., Anderson, E.J., Zeczycki, T.N., Brown, D.A., and Shaikh, S.R. (2018) Docosahexaenoic acid lowers cardiac mitochondrial enzyme activity by replacing linoleic acid in the phospholipidome, J. Biol. Chem., 293, 466–483, doi: 10.1074/jbc.M117.812834.

69. Barth, P.G., Scholte, H.R., Berden, J.A., Van der Klei-Van Moorsel, J.M., Luyt-Houwen, I.E., Van’t Veer-Korthof, E.T., Van der Harten, J.J., and Sobotka-Plojhar, M.A. (1983) An X-linked mitochondrial disease affecting cardiac muscle, skeletal muscle and neutrophil leucocytes, J. Neurol. Sci., 62, 327–355, doi: 10.1016/0022-510x(83)90209-5.

70. Bione, S., D’Adamo, P., Maestrini, E., Gedeon, A.K., Bolhuis, P.A., and Toniolo, D. (1996) A novel X-linked gene, G4.5. is responsible for Barth syndrome, Nat. Genet., 12, 385–389, doi: 10.1038/ng0496-385.

71. Schlame, M., Kelley, R.I., Feigenbaum, A., Towbin, J.A., Heerdt, P.M., Schieble, T., Wanders, R.J.A., DiMauro, S., and Blanck, T.J.J. (2003) Phospholipid abnormalities in children with Barth syndrome, J. Am. Coll. Cardiol., 42, 1994–1999, doi: 10.1016/j.jacc.2003.06.015.

72. Vreken, P., Valianpour, F., Nijtmans, L.G., Grivell, L.A., Plecko, B., Wanders, R.J., and Barth, P.G. (2000) Defective remodeling of cardiolipin and phosphatidylglycerolin Barth syndrome, Biochem. Biophys. Res. Commun., 279, 378–382, doi: 10.1006/bbrc.2000.3952.

73. Acehan, D., Vaz, F., Houtkooper, R.H., James, J., Moore, V., Tokunaga, C., Kulik, W., Wansapura, J., Toth, M.J., Strauss, A., and Khuchua, Z. (2011) Cardiac and skeletal muscle defects in a mouse model of human Barth syndrome, J. Biol. Chem., 286, 899–908, doi: 10.1074/jbc.M110.171439.

74. Shilovsky, G.A., Zverkov, O.A., Seliverstov, A.V., Ashapkin, V.V., Putyatina, T.S., Rubanov, L.I., and Lyubetsky, V.A. (2019) New C-terminal conserved regions of tafazzin, a catalyst of cardiolipin remodeling, Oxid. Med. Cell. Longev., 2019, 2901057, doi: 10.1155/2019/2901057.

75. Tocchi, A., Quarles, E.K., Basisty, N., Gitari, L., and Rabinovitch, P.S. (2015) Mitochondrial dysfunction in cardiac aging, Biochim. Biophys. Acta, 1847, 1424–1433, doi: 10.1016/j.bbabio.2015.07.009.

76. Kirwin, S.M., Manolakos, A., Barnett, S.S., and Gonzalez, I.L. (2014) Tafazzin splice variants and mutations in Barth syndrome, Mol. Genet. Metab., 111, 26–32, doi: 10.1016/j.ymgme.2013.11.006.

77. Xu, Y., Zhang, S., Malhotra, A., Edelman-Novemsky, I., Ma, J., Kruppa, A., Cernicica, C., Blais, S., Neubert, T.A., Ren, M., and Schlame, M. (2009) Characterization of tafazzin splice variants from humans and fruit flies, J. Biol. Chem., 284, 29230–29239, doi: 10.1074/jbc.M109.016642.

78. Ronvelia, D., Greenwood, J., Platt, J., Hakim, S., and Zaragoza, M.V. (2012) Intrafamilial variability for novel TAZ gene mutation: Barth syndrome with dilated cardiomyopathy and heart failure in an infant and left ventricular noncompaction in his great-uncle, Mol. Genet. Metab., 107, 428–432, doi: 10.1016/j.ymgme.2012.09.013.

79. Acehan, D., Xu, Y., Stokes, D.L., and Schlame, M. (2007) Comparison of lymphoblast mitochondria from normal subjects and patients with Barth syndrome using electron microscopic tomography, Lab. Invest., 87, 40–48, doi: 10.1038/labinvest.3700480.

80. Bissler, J.J., Tsorads, M., Goring, H.H., Hug, P., Chuck, G., Tombragel, E., McGraw, C., Schlotman, J., Ralston, M.A., and Hug, G. (2002) Infantile dilated X-linked cardiomyopathy, G4.5 mutations, altered lipids, and ultrastructural malformations of mitochondria in heart, liver, and skeletal muscle, Lab. Invest., 82, 335–344, doi: 10.1038/labinvest.3780427.

81. Huang, Y., Powers, C., Madala, S.K., Greis, K.D., Haffey, W.D., Towbin, J.A., Purevjav, E., Javadov, S., Strauss, A.W., and Khuchua, Z. (2015) Cardiac metabolic pathways affected in the mouse model of Barth syndrome, PLoS One, 10, e0128561, doi: 10.1371/journal.pone.0128561.

82. Kiebish, M.A., Yang, K., Liu, X., Mancuso, D.J., Guan, S., Zhao, Z., Sims, H.F., Cerqua, R., Cade, W.T., Han, X., and Gross, R.W. (2013) Dysfunctional cardiac mitochondrial bioenergetic, lipidomic, and signaling in a murine model of Barth syndrome, J. Lipid Res., 54, 1312–1325, doi: 10.1194/jlr.M034728.

83. Gawrisch, K. (2012) Tafazzin senses curvature, Nat. Chem. Biol., 8, 811–812, doi: 10.1038/nchembio.1068.

84. Chicco, A.J., and Sparagna, G.C. (2007) Role of cardiolipin alterations in mitochondrial dysfunction and disease, Am. J. Physiol., 292, 33–44, doi: 10.1152/ajpcell.00243.2006.

85. Han, X., Yang, J., Yang, K., Zhao, Z., Abendschein, D.R., and Gross, R.W. (2007) Alterations in myocardial cardiolipin content and composition occur at the very earliest stages of diabetes: a shotgun lipidomics study, Biochemistry, 46, 6417–6428, doi: 10.1021/bi7004015.

86. Sparagna, G.C., Chicco, A.J., Murphy, R.C., Bristow, M.R., Johnson, C.A., Rees, M.L., Maxey, M.L., McCune, S.A., and Moore, R.L. (2007) Loss of cardiac tetralinoleoyl cardiolipin in human and experimental heart failure, J. Lipid Res., 48, 1559–1570, doi: 10.1194/jlr.M600551-JLR200.

87. Almaida-Pagan, P.F., Lucas-Sanchez, A., and Tocher, D.R. (2014) Changes in mitochondrial membrane composition and oxidative status during rapid growth, maturation and aging in zebrafish, Danio rerio, Biochim. Biophys. Acta, 1841, 1003–1011, doi: 10.1016/j.bbalip.2014.04.004.

88. Aluri, H.S., Simpson, D.C., Allegood, J.C., Hu, Y., Szczepanek, K., Gronert, S., Chen, Q., and Lesnefsky, E.J. (2014) Electron flow into cytochrome c coupled with reactive oxygen species from the electron transport chain converts cytochrome c to a cardiolipin peroxidase: role during ischemia-reperfusion, Biochim. Biophys. Acta, 1840, 3199–3207, doi: 10.1016/j.bbagen.2014.07.017.

89. Modi, H.R., Katyare, S.S., and Patel, M.A. (2008) Ageing-induced alterations in lipid/phospholipid profiles of rat brain and liver mitochondria: implications for mitochondrial energy linked functions, J. Membr. Biol., 221, 51–60, doi: 10.1007/s00232-007-9086-0.

90. Liu, X., Ye, B., Miller, S., Yuan, H., Zhang, H., Tian, L., Nie, J., Imae, R., Arai, H., Li, Y., Cheng, Z., and Shi, Y. (2012) Ablation of ALCAT1 mitigates hypertrophic cardiomyopathy through effects onoxidative stress and mitophagy, Mol. Cell. Biol., 32, 4493–4504, doi: 10.1128/MCB.01092-12.

91. Paradies, G., Petrosillo, G., Gadaleta, M.N., and Ruggiero, F.M. (1999) The effect of aging and acetyl-L-carnitine on the pyruvate transport and oxidation in rat heart mitochondria, FEBS Lett., 454, 207–209, doi: 10.1016/s0014-5793(99)00809-1.

92. Pepe, S., Tsuchiya, N., Lakatta, E.G., and Hansford, R.G. (1999) PUFA and aging modulate cardiac mitochondrial membrane lipid composition and Ca2+ activation of PDH, Am. J. Physiol., 276, 149–158, doi: 10.1152/ajpheart.1999.276.1.H149.

93. Tamburini, I., Quartacci, M.F., Izzo, R., and Bergamini, E. (2004) Effects of dietary restriction on age-related changes in the phospholipid fatty acid composition of various rat tissues, Aging Clin. Exp. Res., 16, 425–431, doi: 10.1007/BF03327396.

94. Paradies, G., Ruggiero, F.M., Petrosillo, G., and Quagliariello, E. (1997) Age-dependent decline in the cytochrome c oxidase activity in rat heart mitochondria, FEBS Lett., 406, 136–138, doi: 10.1016/s0014-5793(97)00264-0.

95. McMillin, J.B., Taffet, G.E., Taegtmeyer, H., Hudson, E.K., and Tate, C.A. (1993) Mitochondrial metabolism and substrate competition in the aging Fischer rat heart, Cardiovasc. Res., 27, 2222–2228, doi: 10.1093/cvr/27.12.2222.

96. Moghaddas, S., Stoll, M.S., Minkler, P.E., Salomon, R.G., and Hoppel, C.L., and Lesnefsky, E.J. (2002) Preservation of cardiolipin content during aging in rat heart interfibrillar mitochondria, J. Gerontol. A Biol. Sci. Med. Sci., 57, 22–28, doi: 10.1093/gerona/57.1.b22.

97. Coleman, G.L., Barthold, S.W., Osbaldiston, G.W., Foster, S.J., and Jonas, A.M. (1977) Pathological changes during aging in barrier-reared Fischer 344 male rats, J. Gerontol., 32, 258–278, doi: 10.1093/geronj/32.3.258.

98. Semba, R.D., Moaddel, R., Zhang, P., Ramsden, C.E., and Ferrucci, L. (2019) Tetra-linoleoyl cardiolipin depletion plays a major role in the pathogenesis of sarcopenia, Med. Hypotheses, 127, 142–149, doi: 10.1016/j.mehy.2019.04.015.

99. Paradies, G., Ruggiero, F.M., Gadaleta, M.N., and Quagliariello, E. (1992) The effect of aging and acetyl-L-carnitine on the activity of the phosphate carrier and on the phospholipid composition in rat heart mitochondria, Biochim. Biophys. Acta, 1103, 324–326, doi: 10.1016/0005-2736(92)90103-s.

100. Monteiro-Cardoso, V.F., Oliveira, M.M., Melo, T., Domingues, M.R., Moreira, P.I, Ferreiro, E., Peixoto, F., and Videira, R.A. (2015) Cardiolipin profile changes are associated to the early synaptic mitochondrial dysfunction in Alzheimer’s disease, J. Alzheimers Dis., 43, 1375–1392, doi: 10.3233/JAD-141002.

101. Petrosillo, G., Ruggiero, F.M., Di Venosa, N., and Paradies, G. (2003) Decreased complex III activity in mitochondria isolated from rat heart subjected to ischemia and reperfusion: role of reactive oxygen species and cardiolipin, FASEB J., 17, 714–716, doi: 10.1096/fj.02-0729fje.

102. Chan, R.B., and Di Paolo, G. (2012) Knockout punch: cardiolipin oxidation in trauma, Nat. Neurosci., 15, 1325–1327, doi: 10.1038/nn.3222.

103. Ting, H.C., Chao, Y.J., and Hsu, Y.H. (2015) Polyunsaturated fatty acids incorporation into cardiolipin in H9c2 cardiac myoblast, J. Nutr. Biochem., 26, 769–775, doi: 10.1016/j.jnutbio.2015.02.005.

104. Chao, Y.J., Chan, J.F., and Hsu, Y.H. (2016) Chemotherapy drug induced discoordination of mitochondrial life cycle detected by cardiolipin fluctuation, PLoS One, 11, e0162457, doi: 10.1371/journal.pone.0162457.

105. Petrosillo, G., Fattoretti, P., Matera, M., Ruggiero, F.M., Bertoni-Freddari, C., and Paradies, G. (2008) Melatonin prevents age-related mitochondrial dysfunction in rat brain via cardiolipin protection, Rejuvenation Res., 11, 935–943, doi: 10.1089/rej.2008.0772.

106. Fink, M.P., Macias, C.A., Xiao, J., Tyurina, Y.Y., Jiang, J., Belikova, N., Delude, R.L., Greenberger, J.S., Kagan, V.E., and Wipf, P. (2007) Hemigramicidin-TEMPO conjugates: novel mitochondria-targeted antioxidants, Biochem. Pharmacol., 74, 801–809, doi: 10.1016/j.bcp.2007.05.019.

107. Szeto, H.H., and Birk, A.V. (2014) Serendipity and the discovery of novel compounds that restore mitochondrial plasticity, Clin. Pharmacol. Ther., 96, 672–683, doi: 10.1038/clpt.2014.174.

108. Kelso, G.F., Porteous, C.M., Coulter, C.V., Hughes, G., Porteous, W.K., Ledgerwood, E.C., Smith, R.A., and Murphy, M.P. (2001) Selective targeting of a redox-active ubiquinone to mitochondria within cells: antioxidant and antiapoptotic properties, J. Biol. Chem., 276, 4588–4596, doi: 10.1074/jbc.M009093200.

109. Antonenko, Y.N., Avetisyan, A.V., Bakeeva, L.E., Chernyak, B.V., Chertkov, V.A., Domnina, L.V., Ivanova, O.Y., Izyumov, D.S., Khailova, L.S., Klishin, S.S., Korshunova, G.A., Lyamzaev, K.G., Muntyan, M.S., Nepryakhina, O.K., Pashkovskaya, A.A., Pletjushkina, O.Y., Pustovidko, A.V., Roginsky, V.A., Rokitskaya, T.I., Ruuge, E.K., Saprunova, V.B., Severina, I.I, Simonyan, R.A., Skulachev, I.V., Skulachev, M.V., Sumbatyan, N.V., Sviryaeva, I.V., Tashlitsky, V.N., Vassiliev, J.M., Vyssokikh, M.Y., Yaguzhinsky, L.S., Zamyatnin, A.A., Jr., and Skulachev, V.P. (2008) Mitochondria-targeted plastoquinone derivatives as tools to interrupt execution of the aging program. 1. Cationic plastoquinone derivatives: synthesis and in vitro studies, Biochemistry (Moscow), 73, 1273–1287, doi: 10.1134/s0006297908120018.

110. Anisimov, V.N., Egorov, M.V., Krasilshchikova, M.S., Lyamzaev, K.G., Manskikh, V.N., Moshkin, M.P., Novikov, E.A., Popovich, I.G., Rogovin, K.A., Shabalina, I.G., Shekarova, O.N., Skulachev, M.V., Titova, T.V., Vygodin, V.A., Vyssokikh, M.Y., Yurova, M.N., Zabezhinsky, M.A., and Skulachev, V.P. (2011) Effects of the mitochondria-targeted antioxidant SkQ1 on lifespan of rodents, Aging (Albany N. Y.), 3, 1110–1119, doi: 10.18632/aging.100404.

111. Lyamzaev, K.G., Pustovidko, A.V., Simonyan, R.A., Rokitskaya, T.I., Domnina, L.V., Ivanova, O.Y., Severina, I.I., Sumbatyan, N.V., Korshunova, G.A., Tashlitsky, V.N., Roginsky, V.A., Antonenko, Y.N., Skulachev, M.V., Chernyak, B.V., and Skulachev, V.P. (2011) Novel mitochondria-targeted antioxidants: plastoquinone conjugated with cationic plant alkaloids berberine and palmatine, Pharm. Res., 28, 2883–2895, doi: 10.1007/s11095-011-0504-8.

112. Skulachev, V.P. (2012) Mitochondria-targeted antioxidants as promising drugs for treatment of age-related brain diseases, J. Alzheimers Dis., 28, 283–289, doi: 10.3233/JAD-2011-111391.

113. Jiang, J., Bakan, A., Kapralov, A.A., Silva, K.I., Huang, Z., Amoscato, A.A., Peterson, J., Garapati, V.K., Saxena, S., Bayir, H., Atkinson, J., Bahar, I., and Kagan, V.E. (2014) Designing inhibitors of cytochrome c/cardiolipin peroxidase complexes: mitochondria-targeted imidazole-substituted fatty acids, Free Radic. Biol. Med., 71, 221–230, doi: 10.1016/j.freeradbiomed.2014.02.029.

114. Kloner, R.A., Hale, S.L., Dai, W., Gorman, R.C., Shuto, T., Koomalsingh, K.J., Gorman, J.H. 3rd, Sloan, R.C., Frasier, C.R., Watson, C.A., Bostian, P.A., Kypson, A.P., and Brown, D.A. (2012) Reduction of ischemia/reperfusion injury with bendavia, a mitochondria-targeting cytoprotective peptide, J. Am. Heart Assoc., 1, e001644, doi: 10.1161/JAHA.112.001644.

115. Szeto, H.H. (2018) Stealth peptides target cellular powerhouses to fight rare and common age-related diseases, Protein Pept. Lett., 25, 1108–1123, doi: 10.2174/0929866525666181101105209.

116. Szeto, H.H. (2014) First-in-class cardiolipin-protective compound as a therapeutic agent to restore mitochondrial bioenergetics, Br. J. Pharmacol., 171, 2029–2050, doi: 10.1111/bph.12461.

117. McLachlan, J., Beattie, E., Murphy, M.P., Koh-Tan, C.H., Olson, E., Beattie, W., Dominiczak, A.F., Nicklin, S.A., and Graham, D. (2014) Combined therapeutic benefit of mitochondria-targeted antioxidant, MitoQ10, and angiotensin receptor blocker, losartan, on cardiovascular function, J. Hypertens., 32, 555–564, doi: 10.1097/HJH.0000000000000054.

118. Adlam, V.J., Harrison, J.C., Porteous, C.M., James, A.M., Smith, R.A., Murphy, M.P., and Sammut, I.A. (2005) Targeting an antioxidant to mitochondria decreases cardiac ischemia-reperfusion injury, FASEB J., 19, 1088–1095, doi: 10.1096/fj.05-3718com.

119. Skulachev, V.P., Antonenko, Y.N., Cherepanov, D.A., Chernyak, B.V., Izyumov, D.S., Khailova, L.S., Klishin, S.S., Korshunova, G.A., Lyamzaev, K.G., Pletjushkina, O.Y., Roginsky, V.A., Rokitskaya, T.I., Severin, F.F., Severina, I.I., Simonyan, R.A., Skulachev, M.V., Sumbatyan, N.V., Sukhanova, E.I., Tashlitsky, V.N., Trendeleva, T.A., Vyssokikh, M.Y., and Zvyagilskaya, R.A. (2010) Prevention of cardiolipin oxidation and fatty acid cycling as two antioxidant mechanisms of cationic derivatives of plastoquinone (SkQs), Biochim. Biophys. Acta, 1797, 878–889, doi: 10.1016/j.bbabio.2010.03.015.

120. Trifunovic, A., Wredenberg, A., Falkenberg, M., Spelbrink, J.N., Rovio, A.T., Bruder, C.E., Bohlooly, Y.M., Gidlöf, S., Oldfors, A., Wibom, R., Törnell, J., Jacobs, H.T., and Larsson, N.G. (2004) Premature ageing in mice expressing defective mitochondrial DNA polymerase, Nature, 429, 417–423, doi: 10.1038/nature02517.

121. Shabalina, I.G., Vyssokikh, M.Y., Gibanova, N., Csikasz, R.I., Edgar, D., Hallden-Waldemarson, A., Rozhdestvenskaya, Z., Bakeeva, L.E., Vays, V.B., Pustovidko, A.V., Skulachev, M.V., Cannon, B., Skulachev, V.P., and Nedergaard, J. (2017) Improved health-span and lifespan in mtDNA mutator mice treated with the mitochondrially targeted antioxidant SkQ1, Aging (Albany NY), 9, 315–339, doi: 10.18632/aging.101174.

122. Lokhmatikov, A.V., Voskoboynikova, N., Cherepanov, D.A., Skulachev, M.V., Steinhoff, H.J., Skulachev, V.P., and Mulkidjanian, A.Y. (2016) Impact of antioxidants on cardiolipin oxidation in liposomes: why mitochondrial cardiolipin serves as an apoptotic signal? Oxid. Med. Cell Longev., 8679469, doi: 10.1155/2016/8679469.

123. Mileykovskaya, E., and Dowhan, W. (2009) Cardiolipin membrane domains in prokaryotes and eukaryotes, Biochim. Biophys. Acta, 1788, 2084–2091, doi: 10.1016/j.bbamem.2009.04.003.

124. Bradley, R.M., Stark, K.D., and Duncan, R.E. (2016) Influence of tissue, diet, and enzymatic remodeling on cardiolipin fatty acyl profile, Mol. Nutr. Food Res., 60, 1804–1818, doi: 10.1002/mnfr.201500966.

125. Broadhurst, C.L., Wang, Y., Crawford, M.A., Cunnane, S.C., Parkington, J.E., and Schmidt, W.F. (2002) Brain-specific lipids from marine, lacustrine, or terrestrial food resources: potential impact on early African Homo sapiens, Comp. Biochem. Physiol. B Biochem. Mol. Biol., 131, 653–673, doi: 10.1016/s1096-4959(02)00002-7.