БИОХИМИЯ, 2019, том 84, вып. 11, с. 1743–1758

УДК 577.152.13

Роль митохондриального комплекса I в повреждении ткани головного мозга после ишемии/реперфузии

Обзор

© 2019 А. Галкин *

Division of Neonatology, Department of Pediatrics, Columbia University William Black Building, 10032 New York, NY USA; E-mail: ag4003@cumc.columbia.edu

Поступила в редакцию 07.06.2019
После доработки 08.07.2019
Принята к публикации 09.07.2019

DOI: 10.1134/S0320972519110150

КЛЮЧЕВЫЕ СЛОВА: инсульт, повреждение в результате ишемии/реперфузии, митохондрии, комплекс I, флавин, тиоловые группы, нитрозилирование.

Аннотация

Ишемический инсульт и неонатальная гипоксически-ишемическая энцефалопатия являются одними из основных причин инвалидности у взрослых людей и новорожденных. Потребности клеток мозга в энергии обеспечиваются за счет механизма окислительного фосфорилирования, протекающего в митохондриях. Синдром ишемии/реперфузии характеризуется нарушением процесса образования АТP в митохондриях, что приводит к гибели клеток мозга из-за недостатка энергии. Митохондриальный комплекс I — ферментативный комплекс дыхательной цепи, характеризующийся наибольшей чувствительностью к ишемии/реперфузии. Механизмы ингибирования этого комплекса до сих пор не достаточно изучены. В настоящем обзоре рассмотрены данные литературы, касающиеся нарушения структуры и функций митохондрий во время ишемии/реперфузии, а также предложены два различных механизма повреждения комплекса I, основанные на результатах последних исследований в лаборатории автора. Одним из механизмов является обратимая диссоциация естественного кофактора фермента флавинмононуклеотида в условиях ишемии. Другой механизм предполагает модификацию ключевого остатка цистеина комплекса I после перехода фермента из активного конформационного состояния в деактивированное (А/Д переход). В представленном обзоре описано потенциальное влияние этих двух процессов на развитие нарушений функционирования митохондрий при ишемии/реперфузии и кратко обсуждаются возможные нейропротекторные стратегии, направленные на снижение степени повреждения клеток при ишемии/реперфузии.

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Сноски

* Автор является выпускником кафедры биохимии биологического факультета МГУ им. М.В. Ломоносова.

Финансирование

Выполнение работы в лаборатории автора было поддержано грантом NS-100850 (NIH USA) и грантами G1100051 и MR/L007339/1 (MRC UK).

Благодарности

Автор работы искренне благодарен своим коллегам Вадиму Тену и Анне Степановой за ценные замечания при подготовке данной работы. Автор выражает благодарность Вере Георгиевне Гривенниковой за помощь в переводе данного обзора на русский язык.

Конфликт интересов

Автор заявляет об отсутствии конфликта интересов.

Соблюдение этических норм

Настоящая статья не содержит каких-либо исследований с участием людей или использованием животных в качестве объектов исследований.

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