Sirt5 improves cardiomyocytes fatty acid metabolism and ameliorates cardiac lipotoxicity in diabetic cardiomyopathy via CPT2 de-succinylation

Wu, Maoxiong; Tan, Jing; Cao, Zhengyu; Cai, Yangwei; Huang, Zhaoqi; Chen, Zhiteng; He, Wanbing; Liu, Xiao; Jiang, Yuan; Gao, Qingyuan; Deng, Bingqing; Wang, Jingfeng; Yuan, Woliang; Zhang, Haifeng; Chen, Yangxin

doi:10.1016/j.redox.2024.103184

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2024

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Cited by 4 publications

References 45 publications

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Epigenetic regulation of diverse regulated cell death modalities in cardiovascular disease: Insights into necroptosis, pyroptosis, ferroptosis, and cuproptosis

Chen,

Wang,

Zhang

et al. 2024

Redox Biology

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Epigenetic regulation of diverse regulated cell death modalities in cardiovascular disease: Insights into necroptosis, pyroptosis, ferroptosis, and cuproptosis

Chen,

Wang,

Zhang

et al. 2024

Redox Biology

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Multi-omics insights into the pathogenesis of diabetic cardiomyopathy: epigenetic and metabolic profiles

Zhou,

Mei,

et al. 2024

Epigenomics

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Sirt5 preserves cardiac function in ischemia-reperfusion injury by inhibiting ANT2 lactylation

Li,

Shen,

Hong

et al. 2024

Preprint

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Myocardial ischemia-reperfusion (IR) injury is the most common type of heart disease. IR-disrupted mitochondrial homeostasis affects heart energy metabolism and function, but the mechanism remains poorly understood. Here we report a cardioprotective role of the mitochondrial protein Sirt5 in a mouse model of cardiac IR injury. The down-regulation of Sirt5 in IR-injured heart is associated with an increased protein lactylation and impaired mitochondrial function. Overexpression of Sirt5 alleviates, whereas conditional knockout of Sirt5 aggravates, mitochondrial damage and cardiac injury. Mechanistically, Sirt5 interacts with the inner mitochondrial membrane protein adenine nucleotide translocase 2 (ANT2), inhibiting its lysine lactylation to promote its association with the outer mitochondrial membrane protein voltage-dependent anion-selective channel 1 (VDAC1). Lactylation-resistant ANT2 efficiently complexes with VDAC1 and improves cardiac function after injury. Therefore, we uncover a Sirt5-regulated interaction of ANT2 and VDAC1 in maintaining mitochondrial homeostasis, highlighting the potential of targeting ANT2 lactylation as a therapeutic strategy in the treatment of cardiac injury.

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Sirt5 improves cardiomyocytes fatty acid metabolism and ameliorates cardiac lipotoxicity in diabetic cardiomyopathy via CPT2 de-succinylation

Cited by 4 publications

References 45 publications

Epigenetic regulation of diverse regulated cell death modalities in cardiovascular disease: Insights into necroptosis, pyroptosis, ferroptosis, and cuproptosis

Epigenetic regulation of diverse regulated cell death modalities in cardiovascular disease: Insights into necroptosis, pyroptosis, ferroptosis, and cuproptosis

Multi-omics insights into the pathogenesis of diabetic cardiomyopathy: epigenetic and metabolic profiles

Sirt5 preserves cardiac function in ischemia-reperfusion injury by inhibiting ANT2 lactylation

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