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  4. T. 57, № 6, 2023

Молекулярная биология, 2023, T. 57, № 6, стр. 1175-1187

Регуляция метаболизма и роль редокс-факторов в энергетическом контроле покоя и пролиферации кроветворных клеток

М. В. Калашникова a, Н. С. Полякова a, А. В. Белявский a, *

a Институт молекулярной биологии им. В.А. Энгельгардта Российской академии наук
119991 Москва, Россия

* E-mail: abelyavs@yahoo.com

Поступила в редакцию 26.04.2023
После доработки 13.06.2023
Принята к публикации 21.06.2023

Аннотация

Клеточный метаболизм относится к ключевым регуляторам поддержания гемопоэтических стволовых клеток (ГСК). Анаэробный гликолиз используется как основной источник энергии у покоящихся ГСК. При экспансии и дифференцировке в условиях стационарного гемопоэза энергетические потребности активированных ГСК многократно возрастают. Для удовлетворения увеличившихся запросов клетки переходят к митохондриальному окислительному фосфорилированию, при этом возрастает производство активных форм кислорода (АФК). В обзоре рассмотрены молекулярные механизмы поддержания гликолиза в ГСК, а также факторы, определяющие увеличение метаболической активности и переход к митохондриальному биогенезу при активации ГСК. Мы останавливаемся на роли белков HIF (hypoxia-inducible factor) как ключевых медиаторов клеточного ответа на гипоксию, а также рассматриваем явление экстрафизиологического кислородного шока/стресса (EPHOSS), приводящего к форсированной дифференцировке ГСК, и методы его преодоления. Наконец, обсуждается роль окисления жирных кислот (FAO) в гемопоэзе. Понимание метаболических потребностей нормальных ГСК и предшественников имеет решающее значение для разработки новых методов лечения заболеваний, связанных с кроветворной и иммунной системами.

Ключевые слова: кроветворение, гемопоэтические стволовые клетки, анаэробный гликолиз, стрессовый гемопоэз, митохондриальный биогенез, окисление жирных кислот, HIF, окислительный стресс, редокс-факторы, активные формы кислорода

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