Mitochondrial fragmentation in early differentiation of human MB135 myoblasts: Role of mitochondrial ROS production in the absence of depolarization

Chernyavskij, D.A.; Lyamzaev, K.G.; Pletjushkina, O.Y.; Chen, F.; Karpukhina, A.; Vassetzky, Y.S.; Chernyak, B.V.; Popova, E.N.

Авторы: Chernyavskij Daniil A., Lyamzaev Konstantin G., Pletjushkina Olga Yu, Chen Fei, Karpukhina Anna, Vassetzky Yegor S., Chernyak Boris V., Popova Ekaterina N.
Журнал: Life Sciences
Том: 354
Год издания: 2024
Издательство: Elsevier BV
Местоположение издательства: Netherlands
Номер статьи: 122941
DOI: 10.1016/j.lfs.2024.122941
Аннотация: AimsStudy of the role of mitochondria-generated reactive oxygen species (mtROS) and mitochondrial polarization in mitochondrial fragmentation at the initial stages of myogenesis.Main methodsMitochondrial morphology, Drp1 protein phosphorylation, mitochondrial electron transport chain components content, mtROS and mitochondrial lipid peroxidation levels, and mitochondrial polarization were evaluated on days 1 and 2 of human MB135 myoblasts differentiation. A mitochondria-targeted antioxidant SkQ1 was used to elucidate the effect of mtROS on mitochondria.Key findingsIn immortalized human MB135 myoblasts, mitochondrial fragmentation began on day 1 of differentiation before the myoblast fusion. This fragmentation was preceded by dephosphorylation of p-Drp1 (Ser-637). On day 2, an increase in the content of some mitochondrial proteins was observed, indicating mitochondrial biogenesis stimulation. Furthermore, we found that myogenic differentiation, even on day 1, was accompanied both by an increased production of mtROS, and lipid peroxidation of the inner mitochondrial membrane. SkQ1 blocked these effects and partially reduced the level of mitochondrial fragmentation, but did not affect the dephosphorylation of p-Drp1 (Ser-637). Importantly, mitochondrial fragmentation at early stages of MB135 differentiation was not accompanied by depolarization, as an important stimulus for mitochondrial fragmentation.SignificanceMitochondrial fragmentation during early myogenic differentiation depends on mtROS production rather than mitochondrial depolarization. SkQ1 only partially inhibited mitochondrial fragmentation, without significant effects on mitophagy or early myogenic differentiation.
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Mitochondrial fragmentation in early differentiation of human MB135 myoblasts: Role of mitochondrial ROS production in the absence of depolarizationстатья

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