Open AccessCaveolin‐1 deficiency induces premature senescence with mitochondrial dysfunction
Author(s) -
Yu DongMin,
Jung Seung Hee,
An HyoungTae,
Lee Sungsoo,
Hong Jin,
Park Jun Sub,
Lee Hyun,
Lee Hwayeon,
Bahn MyeongSuk,
Lee Hyung Chul,
Han NaKyung,
Ko Jesang,
Lee JaeSeon,
Ko YoungGyu
Publication year - 2017
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12606
Subject(s) - cardiolipin , senescence , biology , mitochondrion , microbiology and biotechnology , gene knockdown , oxidative phosphorylation , reactive oxygen species , caveolin 1 , apoptosis , genetics , biochemistry , phospholipid , membrane
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, HCT 116, 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 SIRT 1, 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 ( SIRT 1) inactivation.