Mitochondrial Oxidative Stress and Mitophagy Activation Contribute to TNF-Dependent Impairment of Myogenesis

Chernyavskij, D.A.; Pletjushkina, O.Y.; Kashtanova, A.V.; Galkin, I.I.; Karpukhina, A.; Chernyak, B.V.; Vassetzky, Y.S.; Popova, E.N.

Авторы: Chernyavskij Daniil A., Pletjushkina Olga Yu, Kashtanova Anastasia V., Galkin Ivan I., Karpukhina Anna, Chernyak Boris V., Vassetzky Yegor S., Popova Ekaterina N.
Журнал: ANTIOXIDANTS
Том: 12
Номер: 3
Год издания: 2023
Первая страница: 602
DOI: 10.3390/antiox12030602
Аннотация: Many muscular pathologies are associated with oxidative stress and elevated levels of thetumor necrosis factor (TNF) that cause muscle protein catabolism and impair myogenesis. Myogenesisdefects caused by TNF are mediated in part by reactive oxygen species (ROS), including thoseproduced by mitochondria (mitoROS), but the mechanism of their pathological action is not fully understood.We hypothesized that mitoROS act by triggering and enhancing mitophagy, an importanttool for remodelling the mitochondrial reticulum during myogenesis. We used three recently developedprobes—MitoTracker Orange CM-H2TMRos, mito-QC, and MitoCLox—to study myogenesisin human myoblasts. Induction of myogenesis resulted in a significant increase in mitoROS generationand phospholipid peroxidation in the inner mitochondrial membrane, as well as mitophagyenhancement. Treatment of myoblasts with TNF 24 h before induction of myogenesis resulted in asignificant decrease in the myoblast fusion index and myosin heavy chain (MYH2) synthesis. TNFincreased the levels of mitoROS, phospholipid peroxidation in the inner mitochondrial membraneand mitophagy at an early stage of differentiation. Trolox and SkQ1 antioxidants partially restoredTNF-impaired myogenesis. The general autophagy inducers rapamycin and AICAR, which also stimulatemitophagy, completely blocked myogenesis. The autophagy suppression by the ULK1 inhibitorSBI-0206965 partially restored myogenesis impaired by TNF. Thus, suppression of myogenesis byTNF is associated with a mitoROS-dependent increase in general autophagy and mitophagy.
Добавил в систему: Попова Екатерина Николаевна

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Mitochondrial Oxidative Stress and Mitophagy Activation Contribute to TNF-Dependent Impairment of Myogenesisстатья

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