title: Mouse Sirt3 promotes autophagy in AngII-induced myocardial hypertrophy through the deacetylation of FoxO1.
abstract: Sirt3, a mitochondrial NAD+-dependent histone deacetylase, is the only member proven to promote longevity in mammalian Sirtuin family. The processed short form of Sirt3 has been demonstrated to target many mediators of energy metabolism and mitochondrial stress adaptive program. Autophagy serves as a dynamic recycling mechanism and provides energy or metabolic substrates. Among the mechanisms triggered by cardiac stress, opinions vary as to whether autophagy is a protective or detrimental response. Here, by inducing the Sirt3-knockout mice to myocardial hypertrophy with chronic angiotensin II infusion for four weeks, we determined the role of Sirt3 in myocardial hypertrophy and autophagy. In this study, the Sirt3-knockout mice developed deteriorated cardiac function and impaired autophagy compared to wild-type mice. What's more, the overexpression of Sirt3 by lentivirus transfection attenuated cardiomyocytes hypertrophy by promoting autophagy. We further demonstrated that Sirt3 could bind to FoxO1 and activate its deacetylation. Sequentially, deacetylated FoxO1 translocates to the nucleus where it facilitates downstream E3 ubiquitin ligases such as Muscle RING Finger 1 (MuRF1) and muscle atrophy F-box (MAFbx, Atrogin1). Altogether, these results revealed that Sirt3 activation is essential to improve autophagy flux by reducing the acetylation modification on FoxO1, which in turn alleviates myocardial hypertrophy.
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, China.
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Li
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, China.
authors.forename: Tongshuai
authors.initials: T
authors.lastname: Chen
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Xiao
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, China.
authors.forename: Shujian
authors.initials: S
authors.lastname: Wang
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Su
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, China.
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Guo
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, China.
authors.forename: Fangying
authors.initials: F
authors.lastname: Yan
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, China.
authors.forename: Peili
authors.initials: P
authors.lastname: Bu
mesh_terms: D000107:Acetylation; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D006332:Cardiomegaly / Q000473:pathology*; D002478:Cells, Cultured; D000071161:Forkhead Box Protein O1 / Q000378:metabolism*; D051379:Mice; D051381:Rats; D056566:Sirtuin 3 / Q000502:physiology*
chemical_list: D000071161:Forkhead Box Protein O1; C467200:Foxo1 protein, mouse; C525046:Sirt3 protein, mouse; D000804:Angiotensin II; D056566:Sirtuin 3
keywords: FoxO1; Sirt3; autophagy; deacetylation modification; myocardial hypertrophy