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 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.
| Original language | English |
|---|---|
| Pages (from-to) | 13-24 |
| Number of pages | 12 |
| Journal | Cellular Signalling |
| Volume | 48 |
| DOIs | |
| Publication status | Published - 2018 Aug |
Fingerprint
All Science Journal Classification (ASJC) codes
- Cell Biology
Cite this
}
S6 kinase 1 plays a key role in mitochondrial morphology and cellular energy flow. / 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.
In: Cellular Signalling, Vol. 48, 08.2018, p. 13-24.Research output: Contribution to journal › Article
TY - JOUR
T1 - S6 kinase 1 plays a key role in mitochondrial morphology and cellular energy flow
AU - Tran, Quangdon
AU - Jung, Jae Hun
AU - Park, Jisoo
AU - Lee, Hyunji
AU - Hong, Youngeun
AU - Cho, Hyeonjeong
AU - Kim, Minhee
AU - Park, Sungjin
AU - Kwon, So Hee
AU - Kim, Seon Hwan
AU - Thomas, George
AU - Kim, Kwang Pyo
AU - Cho, Myung Haing
AU - Park, Jongsun
PY - 2018/8
Y1 - 2018/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85046168833&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85046168833&partnerID=8YFLogxK
U2 - 10.1016/j.cellsig.2018.04.002
DO - 10.1016/j.cellsig.2018.04.002
M3 - Article
C2 - 29673648
AN - SCOPUS:85046168833
VL - 48
SP - 13
EP - 24
JO - Cellular Signalling
JF - Cellular Signalling
SN - 0898-6568
ER -