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, Je Sang Ko, Jae Seon Lee, Young-Gyu Ko

Research output: Contribution to journalArticle

12 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 languageEnglish
JournalAging Cell
DOIs
Publication statusAccepted/In press - 2017

Fingerprint

Caveolin 1
Cell Aging
Cardiolipins
NAD
Respiration
Fibroblasts
Oxidative Phosphorylation
Diploidy
Reactive Oxygen Species
Down-Regulation
Lipids
Enzymes

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 journalArticle

Yu, DM, Jung, SH, An, HT, Lee, S, Hong, J, Park, JS, Lee, H, Lee, H, Bahn, MS, Lee, HC, Han, NK, Ko, JS, Lee, JS & Ko, Y-G 2017, 'Caveolin-1 deficiency induces premature senescence with mitochondrial dysfunction', Aging Cell. https://doi.org/10.1111/acel.12606
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. / Caveolin-1 deficiency induces premature senescence with mitochondrial dysfunction. In: Aging Cell. 2017.
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