Caveolin-1 deficiency induces premature senescence with mitochondrial dysfunction.
Aging Cell
; 16(4): 773-784, 2017 08.
Article
em En
| MEDLINE
| ID: mdl-28514055
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Senescência Celular
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Caveolina 1
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Sirtuína 1
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Fibroblastos
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Mitocôndrias
Limite:
Animals
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Humans
Idioma:
En
Revista:
Aging Cell
Ano de publicação:
2017
Tipo de documento:
Article