SUMOylation targeting mitophagy in cardiovascular diseases

AbstractSmall ubiquitin-like modifier (SUMO) plays a key regulatory role in cardiovascular diseases, such as cardiac hypertrophy, hypertension, atherosclerosis, and cardiac ischemia –reperfusion injury. As a multifunctional posttranslational modification molecule in eukaryotic cells, SUMOylation is essentially associated with the regulation of mitochondrial dynamics, especially mitophagy, which is involved in the progression and development of cardiovascular diseases. SUMOyla tion targeting mitochondrial-associated proteins is admittedly considered to regulate mitophagy activation and mitochondrial functions and dynamics, including mitochondrial fusion and fission. SUMOylation triggers mitochondrial fusion to promote mitochondrial dysfunction by modifying Fis1, OPA1, MFN 1/2, and DRP1. The interaction between SUMO and DRP1 induces SUMOylation and inhibits lysosomal degradation of DRP1, which is further involved in the regulation of mitochondrial fission. Both SUMOylation and deSUMOylation contribute to the initiation and activation of mitophagy by regulating the con jugation of MFN1/2 SERCA2a, HIF1α, and PINK1. SUMOylation mediated by the SUMO molecule has attracted much attention due to its dual roles in the development of cardiovascular diseases. In this review, we systemically summarize the current understanding underlying the expression, regulation, and st ructure of SUMO molecules; explore the biochemical functions of SUMOylation in the initiation and activation of mi...
Source: Journal of Molecular Medicine - Category: Molecular Biology Source Type: research