Caveolin-1 deficiency induces premature senescence with mitochondrial dysfunction

Dong Min Yu; Seung Hee Jung; Hyoung Tae An; Sungsoo Lee; Jin Hong; Jun Sub Park; Hyun Lee; Hwayeon Lee; Myeong Suk Bahn; Hyung Chul Lee; Na Kyung Han; Jesang Ko; Jae Seon Lee; Young Gyu Ko

doi:10.1111/acel.12606

Caveolin-1 deficiency induces premature senescence with mitochondrial dysfunction

Dong Min Yu, Seung Hee Jung, Hyoung Tae An, Sungsoo Lee, Jin Hong, Jun Sub Park, Hyun Lee, Hwayeon Lee, Myeong Suk Bahn, Hyung Chul Lee, Na Kyung Han, Jesang Ko, Jae Seon Lee, Young Gyu Ko

Research output: Contribution to journal › Article › peer-review

27 Citations (Scopus)

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
Pages (from-to)	773-784
Number of pages	12
Journal	Aging Cell
Volume	16
Issue number	4
DOIs	https://doi.org/10.1111/acel.12606
Publication status	Published - 2017 Aug

Keywords

SIRT1
cardiolipin
caveolin-1
mitochondria
senescence

ASJC Scopus subject areas

Ageing
Cell Biology

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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, Jesang; Lee, Jae Seon; Ko, Young Gyu.

In: Aging Cell, Vol. 16, No. 4, 08.2017, p. 773-784.

Research output: Contribution to journal › Article › peer-review

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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.",

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author = "Yu, {Dong Min} and Jung, {Seung Hee} and An, {Hyoung Tae} and Sungsoo Lee and Jin Hong and Park, {Jun Sub} and Hyun Lee and Hwayeon Lee and Bahn, {Myeong Suk} and Lee, {Hyung Chul} and Han, {Na Kyung} and Jesang Ko and Lee, {Jae Seon} and Ko, {Young Gyu}",

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AU - Ko, Jesang

AU - Lee, Jae Seon

AU - Ko, Young Gyu

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PY - 2017/8

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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.

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Caveolin-1 deficiency induces premature senescence with mitochondrial dysfunction

Abstract

Keywords

ASJC Scopus subject areas

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