Caveolin‐1 deficiency induces premature senescence with mitochondrial dysfunction |
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| Authors: | 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 |
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| Affiliation: | 1. Tunneling Nanotube Research Center, Korea University, Seoul, Korea;2. Division of Life Sciences, Korea University, Seoul, Korea;3. Department of Molecular Medicine, Inha University College of Medicine, Incheon, Korea;4. Hypoxia‐related Disease Research Center, Inha University College of Medicine, Incheon, Korea |
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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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| Keywords: | cardiolipin caveolin‐1 mitochondria senescence SIRT1 |
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