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REVIEW: Biological Diversity and Remodeling of Cardiolipin in Oxidative Stress and Age-Related Pathologies

G. A. Shilovsky1,2,3,a,b*, T. S. Putyatina2, V. V. Ashapkin1, O. V. Yamskova4, V. A. Lyubetsky3, E. V. Sorokina2, S. I. Shram5, A. V. Markov2, and M. Y. Vyssokikh1

1Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia

2Lomonosov Moscow State University, Faculty of Biology, 119234 Moscow, Russia

3Institute for Information Transmission Problems, Russian Academy of Sciences, 127051 Moscow, Russia

4Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 119991 Moscow, Russia

5Institute of Molecular Genetics, Russian Academy of Sciences, 123182 Moscow, Russia

* To whom correspondence should be addressed.

Received August 13, 2019; Revised September 20, 2019; Accepted September 20, 2019
Age-related dysfunctions are accompanied by impairments in the mitochondrial morphology, activity of signaling pathway, and protein interactions. Cardiolipin is one of the most important phospholipids that maintains the curvature of the cristae and facilitates assembly and interaction of complexes and supercomplexes of the mitochondrial respiratory chain. The fatty acid composition of cardiolipin influences the biophysical properties of the membrane and, therefore, is crucial for the mitochondrial bioenergetics. The presence of unsaturated fatty acids in cardiolipin is the reason of its susceptibility to oxidative damage. Damaged cardiolipin undergoes remodeling by phospholipases, acyltransferases, and transacylases, creating a highly specific fatty acyl profile for each tissue. In this review, we discuss the variability of cardiolipin fatty acid composition in various species and different tissues of the same species, both in the norm and at various pathologies (e.g., age-related diseases, oxidative and traumatic stresses, knockouts/knockdowns of enzymes of the cardiolipin synthesis pathway). Progressive pathologies, including age-related ones, are accompanied by cardiolipin depletion and decrease in the efficiency of its remodeling, as well as the activation of an alternative way of pathological remodeling, which causes replacement of cardiolipin fatty acids with polyunsaturated ones (e.g., arachidonic or docosahexaenoic acids). Drugs or special diet can contribute to the partial restoration of the cardiolipin acyl profile to the one rich in fatty acids characteristic of an intact organ or tissue, thereby correcting the consequences of pathological or insufficient cardiolipin remodeling. In this regard, an urgent task of biomedicine is to study the mechanism of action of mitochondria-targeted antioxidants effective in the treatment of age-related pathologies and capable of accumulating not only in vitro, but also in vivo in the cardiolipin-enriched membrane fragments.
KEY WORDS: reactive oxygen species, cardiolipin, tafazzin, mitochondria-targeted antioxidants, lipid peroxidation, aging

DOI: 10.1134/S000629791912006X