Huang, W., Ding, M., Yi, Q., Li, Y., Gu, W., Zhang, P., Tian, R., Zhang, Z., Zheng, L. (2026). Regular exercise improves cardiac dysfunction in Drosophila by inhibiting excessive mitochondrial fission through RalA.  Biochim Biophys Acta Mol Basis Dis 1872(7): 168338.

FBrf0265871

Research paper

Metabolic disorders leading to cardiac dysfunction have become a global health challenge, and the cardioprotective mechanisms of regular exercise remain unclear. This study focused on the small GTPase RalA and revealed its critical role in exercise-mediated improvement of high-fat-induced cardiac dysfunction. Using a high-fat-fed drosophila heart model, combined with genetic manipulation and exercise intervention, it was demonstrated that a high-fat diet upregulates RalA expression in the myocardium, accompanied by excessive mitochondrial fission and impaired cardiac function. Regular exercise not only effectively reversed these pathological phenotypes but also exerted its protective effects in a RalA -dependent manner within the myocardium. Mechanistically, RalA appeared to exert its effects not through traditional energy metabolism pathways, but rather through the regulation of Drp1-mediated mitochondrial fission, thereby preserving mitochondrial network homeostasis and energy supply in cardiomyocytes. This study is the first to propose a novel "exercise-RalA-mitochondrial dynamics" signaling axis, providing new mechanistic insight into the cardioprotective effects of exercise and suggesting that targeting the RalA pathway may represent a promising therapeutic strategy for metabolic heart disease.