Please use this identifier to cite or link to this item: http://hdl.handle.net/10316/14369
Title: Regulation of the mPTP by SIRT3-mediated deacetylation of CypD at lysine 166 suppresses age-related cardiac hypertrophy
Authors: Hafner, Angela V. 
Dai, Jing 
Gomes, Ana P. 
Xiao, Chun-Yang 
Palmeira, Carlos M. 
Keywords: Sirtuin; Mitochondria; Acetylation; Cardiac; Mitochondrial permeability transition; MPTP; Obesity; Calorie restriction
Issue Date: Nov-2010
Publisher: Impact Journals
Citation: HAFNER, Angela V. [et al.] - Regulation of the mPTP by SIRT3-mediated deacetylation of CypD at lysine 166 suppresses age-related cardiac hypertrophy. "Aging". ISSN 1945-4589. 2:12 (2010) 914-923
Serial title, monograph or event: Aging
Volume: 2
Issue: 12
Abstract: Cardiac failure is a leading cause of age-related death, though its root cause remains unknown. Mounting evidence implicates a decline in mitochondrial function due to increased opening of the mitochondrial permeability transition pore (mPTP). Here we report that the NAD+-dependent deacetylase SIRT3 deacetylates the regulatory component of the mPTP, cyclophilin D (CypD) on lysine 166, adjacent to the binding site of cyclosporine A, a CypD inhibitor. Cardiac myocytes from mice lacking SIRT3 exhibit an age-dependent increase in mitochondrial swelling due to increased mPTP opening, a phenotype that is rescued by cyclosporine A. SIRT3 knockout mice show accelerated signs of aging in the heart including cardiac hypertrophy and fibrosis at 13 months of age. SIRT3 knockout mice are also hypersensitive to heart stress induced by transverse aortic constriction (TAC), as evidenced by cardiac hypertrophy, fibrosis, and increased mortality. Together, these data show for the first time that SIRT3 activity is necessary to prevent mitochondrial dysfunction and cardiac hypertrophy during aging and shed light on new pharmacological approaches to delaying aging and treating diseases in cardiac muscle and possibly other post-mitotic tissues.
URI: http://hdl.handle.net/10316/14369
ISSN: 1945-4589
Rights: openAccess
Appears in Collections:FCTUC Ciências da Vida - Artigos em Revistas Internacionais

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