Relationship between Cellular Oxygen Consumption and Atherosclerosis-Associated Mitochondrial Mutations (Variants of the Mitochondrial Genome).

Autor:	Orekhov AN; Institute for Atherosclerosis Research, Moscow, Russsia., Sinyov VV; Institute for Atherosclerosis Research / Institute of General Pathology and Pathophysiology, Moscow, Russsia., Vyssokikh MY; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russsia; Moscow, Russsia., Manukhova L; Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology., Marey MV; Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology., Angelova PR; Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK., Omelchenko AV; Institute for Atherosclerosis Research / Institute of General Pathology and Pathophysiology, Moscow, Russsia., Vinokurov AY; Cell Physiology & Pathology Laboratory of R&D Center of Biomedical Photonics, Orel State University, Orel, Russsia., Khasanova ZB; National Medical Research Center of Cardiology, Moscow, Russsia., Sobenin IA; National Medical Research Center of Cardiology, Moscow, Russsia.
Jazyk:	angličtina
Zdroj:	Current medicinal chemistry [Curr Med Chem] 2024 Jun 14. Date of Electronic Publication: 2024 Jun 14.
DOI:	10.2174/0109298673302002240605092523
Abstrakt:	Background: Mitochondria are the main sites of cellular aerobic energy production through conjugation of respiration and oxidative phosphorylation. We have recently discovered mutations (genome variants) of mitochondrial DNA (mtDNA) associated with atherosclerosis. We have then investigated the possible mechanisms underlying such association and the role of mitochondrial mutations in atherogenesis. Mitochondrial dysfunction is a known component of the pathogenesis of chronic human diseases, including atherosclerosis. Objective: The aim of the study was to explore whether there is a relationship between cellular oxygen consumption and atherosclerosis-associated mitochondrial mutations. The study of mitochondrial respiration abnormalities can help to understand the role of mtDNA mutations in pathology. Method: By using the polarographic method with Clark electrode, we tested the possibility of respiration impairment in permeabilized cells carrying the tested mtDNA variants using the cybrid (cytoplasmic hybrid) lines. Mitochondria introduced in the cybrid lines were obtained from atherosclerotic patients that differed in the profile of mtDNA mutations, which made it possible to compare the degree of mtDNA mutation load with the rate of oxygen consumption by cybrid cells. Results: It was found that three of the studied mutations were individually associated with impaired respiration. Besides, some combinations of two specific mutations have a high probability of being associated with altered oxygen consumption. As a result, eight mutations were identified, individually or paired combinations of which were associated with high or low rates of cellular respiration, significantly different from control cells. Conclusion: The observed effect may be involved in the pathogenesis of atherosclerosis. The study of mtDNA mutations associated with atherosclerosis can help reveal pharmacological targets for the development of novel therapies. (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
Databáze:	MEDLINE
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