Abstract
Paradoxical observations have been made regarding the role of caveolin-1 (Cav-1) during cellular senescence. For example, caveolin-1 deficiency prevents reactive oxygen species-induced cellular senescence despite mitochondrial dysfunction, which leads to senescence. To resolve this paradox, we re-addressed the role of caveolin-1 in cellular senescence in human diploid fibroblasts, A549, HCT116, and Cav-1-/- mouse embryonic fibroblasts. Cav-1 deficiency (knockout or knockdown) induced cellular senescence via a p53-p21-dependent pathway, downregulating the expression level of the cardiolipin biosynthesis enzymes and then reducing the content of cardiolipin, a critical lipid for mitochondrial respiration. Our results showed that Cav-1 deficiency decreased mitochondrial respiration, reduced the activity of oxidative phosphorylation complex I (CI), inactivated SIRT1, and decreased the NAD+/NADH ratio. From these results, we concluded that Cav-1 deficiency induces premature senescence via mitochondrial dysfunction and silent information regulator 2 homologue 1 (SIRT1) inactivation.
| Original language | English |
|---|---|
| Journal | Aging Cell |
| DOIs | |
| Publication status | Accepted/In press - 2017 |
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Keywords
- Cardiolipin
- Caveolin-1
- Mitochondria
- Senescence
- SIRT1
ASJC Scopus subject areas
- Ageing
- Cell Biology
Cite this
Caveolin-1 deficiency induces premature senescence with mitochondrial dysfunction. / Yu, Dong Min; Jung, Seung Hee; An, Hyoung Tae; Lee, Sungsoo; Hong, Jin; Park, Jun Sub; Lee, Hyun; Lee, Hwayeon; Bahn, Myeong Suk; Lee, Hyung Chul; Han, Na Kyung; Ko, Je Sang; Lee, Jae Seon; Ko, Young-Gyu.
In: Aging Cell, 2017.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Caveolin-1 deficiency induces premature senescence with mitochondrial dysfunction
AU - Yu, Dong Min
AU - Jung, Seung Hee
AU - An, Hyoung Tae
AU - Lee, Sungsoo
AU - Hong, Jin
AU - Park, Jun Sub
AU - Lee, Hyun
AU - Lee, Hwayeon
AU - Bahn, Myeong Suk
AU - Lee, Hyung Chul
AU - Han, Na Kyung
AU - Ko, Je Sang
AU - Lee, Jae Seon
AU - Ko, Young-Gyu
PY - 2017
Y1 - 2017
N2 - Paradoxical observations have been made regarding the role of caveolin-1 (Cav-1) during cellular senescence. For example, caveolin-1 deficiency prevents reactive oxygen species-induced cellular senescence despite mitochondrial dysfunction, which leads to senescence. To resolve this paradox, we re-addressed the role of caveolin-1 in cellular senescence in human diploid fibroblasts, A549, HCT116, and Cav-1-/- mouse embryonic fibroblasts. Cav-1 deficiency (knockout or knockdown) induced cellular senescence via a p53-p21-dependent pathway, downregulating the expression level of the cardiolipin biosynthesis enzymes and then reducing the content of cardiolipin, a critical lipid for mitochondrial respiration. Our results showed that Cav-1 deficiency decreased mitochondrial respiration, reduced the activity of oxidative phosphorylation complex I (CI), inactivated SIRT1, and decreased the NAD+/NADH ratio. From these results, we concluded that Cav-1 deficiency induces premature senescence via mitochondrial dysfunction and silent information regulator 2 homologue 1 (SIRT1) inactivation.
AB - Paradoxical observations have been made regarding the role of caveolin-1 (Cav-1) during cellular senescence. For example, caveolin-1 deficiency prevents reactive oxygen species-induced cellular senescence despite mitochondrial dysfunction, which leads to senescence. To resolve this paradox, we re-addressed the role of caveolin-1 in cellular senescence in human diploid fibroblasts, A549, HCT116, and Cav-1-/- mouse embryonic fibroblasts. Cav-1 deficiency (knockout or knockdown) induced cellular senescence via a p53-p21-dependent pathway, downregulating the expression level of the cardiolipin biosynthesis enzymes and then reducing the content of cardiolipin, a critical lipid for mitochondrial respiration. Our results showed that Cav-1 deficiency decreased mitochondrial respiration, reduced the activity of oxidative phosphorylation complex I (CI), inactivated SIRT1, and decreased the NAD+/NADH ratio. From these results, we concluded that Cav-1 deficiency induces premature senescence via mitochondrial dysfunction and silent information regulator 2 homologue 1 (SIRT1) inactivation.
KW - Cardiolipin
KW - Caveolin-1
KW - Mitochondria
KW - Senescence
KW - SIRT1
UR - http://www.scopus.com/inward/record.url?scp=85019220371&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85019220371&partnerID=8YFLogxK
U2 - 10.1111/acel.12606
DO - 10.1111/acel.12606
M3 - Article
C2 - 28514055
AN - SCOPUS:85019220371
JO - Aging Cell
JF - Aging Cell
SN - 1474-9718
ER -