S6 kinase 1 plays a key role in mitochondrial morphology and cellular energy flow

Mitochondrial morphology, which is associated with changes in metabolism, cell cycle, cell development and cell death, is tightly regulated by the balance between fusion and fission. In this study, we found that S6 kinase 1 (S6K1) contributes to mitochondrial dynamics, homeostasis and function. Mous...

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Bibliographic Details
Published in:Cellular signalling 2018-08, Vol.48, p.13-24
Main Authors: Tran, Quangdon, Jung, Jae-Hun, Park, Jisoo, Lee, Hyunji, Hong, Youngeun, Cho, Hyeonjeong, Kim, Minhee, Park, Sungjin, Kwon, So-Hee, Kim, Seon-Hwan, Thomas, George, Kim, Kwang Pyo, Cho, Myung-Haing, Park, Jongsun
Format: Article
Language:English
Subjects:
Drp1
Fission
Metabolic shift
Mitophagy
OxPhos
S6K1
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Summary:Mitochondrial morphology, which is associated with changes in metabolism, cell cycle, cell development and cell death, is tightly regulated by the balance between fusion and fission. In this study, we found that S6 kinase 1 (S6K1) contributes to mitochondrial dynamics, homeostasis and function. Mouse embryo fibroblasts lacking S6K1 (S6K1-KO MEFs) exhibited more fragmented mitochondria and a higher level of Dynamin related protein 1 (Drp1) and active Drp1 (pS616) in both whole cell extracts and mitochondrial fraction. In addition, there was no evidence for autophagy and mitophagy induction in S6K1 depleted cells. Glycolysis and mitochondrial respiratory activity was higher in S6K1-KO MEFs, whereas OxPhos ATP production was not altered. However, inhibition of Drp1 by Mdivi1 (Drp1 inhibitor) resulted in higher OxPhos ATP production and lower mitochondrial membrane potential. Taken together the depletion of S6K1 increased Drp1-mediated fission, leading to the enhancement of glycolysis. The fission form of mitochondria resulted in lower yield for OxPhos ATP production as well as in higher mitochondrial membrane potential. Thus, these results have suggested a potential role of S6K1 in energy metabolism by modulating mitochondrial respiratory capacity and mitochondrial morphology. •S6 kinase 1 contributes to mitochondrial dynamics, homeostasis and function.•Glycolysis and mitochondrial respiratory activity was higher in S6K1-KO MEFs.•The depletion of S6K1 increased Drp1-mediated fission.•The fission form of mitochondria in S6K1-KO MEFs resulted in lower yield for OxPhos ATP production.
ISSN:0898-6568
1873-3913
DOI:10.1016/j.cellsig.2018.04.002