Caveolin‐1 deficiency induces premature senescence with mitochondrial dysfunction

Summary 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,...

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Bibliographic Details
Published in:Aging cell 2017-08, Vol.16 (4), p.773-784
Main Authors: 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, Jesang, Lee, Jae‐Seon, Ko, Young‐Gyu
Format: Article
Language:English
Subjects:
A549 Cells
Animals
Cardiolipin
Cardiolipins - biosynthesis
Caveolin
Caveolin 1 - deficiency
Caveolin 1 - genetics
Caveolin-1
Cellular Senescence - genetics
Cyclin-Dependent Kinase Inhibitor p21 - genetics
Cyclin-Dependent Kinase Inhibitor p21 - metabolism
Electron transport
Electron transport chain
Embryo fibroblasts
Embryo, Mammalian
Embryos
Enzymes
Fibroblasts
Fibroblasts - metabolism
Fibroblasts - pathology
Gene expression
Gene Expression Regulation
Genes
GTP-binding protein
HCT116 Cells
Humans
Mice
Mitochondria
Mitochondria - metabolism
Mitochondria - pathology
Mitochondrial DNA
NAD
NAD - metabolism
NADH
Original
Oxidative Phosphorylation
p53 Protein
Phosphorylation
Primary Cell Culture
Reactive oxygen species
Respiration
Senescence
Signal Transduction
SIRT1
SIRT1 protein
Sirtuin 1 - genetics
Sirtuin 1 - metabolism
Tumor proteins
Tumor Suppressor Protein p53 - genetics
Tumor Suppressor Protein p53 - metabolism
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Summary:Summary 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.
ISSN:1474-9718
1474-9726
DOI:10.1111/acel.12606