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

Cited 8 time in Web of Science Cited 6 time in Scopus
Authors
Quangdon Tran; 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
Issue Date
2018-08
Citation
Cellular Signalling, Vol.48, pp.13-24
Keywords
S6K1Drp1FissionMetabolic shiftMitophagyOxPhos
Abstract
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 mitochondria' 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 Drpl-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.
ISSN
0898-6568
URI
https://hdl.handle.net/10371/172361
DOI
https://doi.org/10.1016/j.cellsig.2018.04.002
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College of Veterinary Medicine (수의과대학)Dept. of Veterinary Medicine (수의학과)Journal Papers (저널논문_수의학과)
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