SOD2
粒体自噬
氧化应激
线粒体
线粒体ROS
活性氧
锡尔图因
细胞生物学
线粒体生物发生
氧化磷酸化
生物
化学
药理学
超氧化物歧化酶
内分泌学
生物化学
细胞凋亡
自噬
乙酰化
基因
作者
Victoriane Peugnet,Maggy Chwastyniak,Paul Mulder,Steve Lancel,Laurent Bultot,Natacha Fourny,Edith Renguet,Heiko Bugger,Olivia Beseme,Anne Loyens,Wilfried Heyse,Vincent Richard,Philippe Amouyel,Luc Bertrand,Florence Pinet,Emilie Dubois‐Deruy
出处
期刊:Antioxidants
[MDPI AG]
日期:2022-04-06
卷期号:11 (4): 723-723
被引量:6
标识
DOI:10.3390/antiox11040723
摘要
Heart failure, mostly associated with cardiac hypertrophy, is a major cause of illness and death. Oxidative stress causes accumulation of reactive oxygen species (ROS), leading to mitochondrial dysfunction, suggesting that mitochondria-targeted therapies could be effective in this context. The purpose of this work was to determine whether mitochondria-targeted therapies could improve cardiac hypertrophy induced by mitochondrial ROS. We used neonatal (NCMs) and adult (ACMs) rat cardiomyocytes hypertrophied by isoproterenol (Iso) to induce mitochondrial ROS. A decreased interaction between sirtuin 3 and superoxide dismutase 2 (SOD2) induced SOD2 acetylation on lysine 68 and inactivation, leading to mitochondrial oxidative stress and dysfunction and hypertrophy after 24 h of Iso treatment. To counteract these mechanisms, we evaluated the impact of the mitochondria-targeted antioxidant mitoquinone (MitoQ). MitoQ decreased mitochondrial ROS and hypertrophy in Iso-treated NCMs and ACMs but altered mitochondrial structure and function by decreasing mitochondrial respiration and mitophagy. The same decrease in mitophagy was found in human cardiomyocytes but not in fibroblasts, suggesting a cardiomyocyte-specific deleterious effect of MitoQ. Our data showed the importance of mitochondrial oxidative stress in the development of cardiomyocyte hypertrophy. We observed that targeting mitochondria by MitoQ in cardiomyocytes impaired the metabolism through defective mitophagy, leading to accumulation of deficient mitochondria.
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