The regenerative capacity of the adult mammalian heart remains a formidable challenge in biological research.Despite extensive investigations into the loss of regenerative potential during evolution and development,un...The regenerative capacity of the adult mammalian heart remains a formidable challenge in biological research.Despite extensive investigations into the loss of regenerative potential during evolution and development,unlocking the mechanisms governing cardiomyocyte proliferation remains elusive.Two recent groundbreaking studies have provided fresh perspectives on mitochondrial-to-nuclear communication,shedding light on novel factors that regu-late cardiomyocyte proliferation.The studies identified two mitochondrial processes,fatty acid oxidation and protein translation,as key players in restricting cardiomyocyte proliferation.Inhibition of these processes led to increased cell cycle activity in cardiomyocytes,mediated by reduction in H3k4me3 levels through accumulatedα-ketoglutarate(αKG),and activation of the mitochondrial unfolded protein response(UPRmt),respectively.In this research highlight,we discuss the novel insights into mitochondrial-to-nuclear communication presented in these studies,the broad implications in cardiomyocyte biology and cardiovascular diseases,as well as the intriguing scientific questions inspired by the studies that may facilitate future investigations into the detailed molecular mechanisms of cardiomyo-cyte metabolism,proliferation,and mitochondrial-to-nuclear communications.展开更多
基金Key Research and Development Program,Ministry of Science and Technology of China(2018YFA0800104)National Natural Science Foundation of China(92168205,32070823)Fundamental Research Funds for the Central Universities(22120230471).
文摘The regenerative capacity of the adult mammalian heart remains a formidable challenge in biological research.Despite extensive investigations into the loss of regenerative potential during evolution and development,unlocking the mechanisms governing cardiomyocyte proliferation remains elusive.Two recent groundbreaking studies have provided fresh perspectives on mitochondrial-to-nuclear communication,shedding light on novel factors that regu-late cardiomyocyte proliferation.The studies identified two mitochondrial processes,fatty acid oxidation and protein translation,as key players in restricting cardiomyocyte proliferation.Inhibition of these processes led to increased cell cycle activity in cardiomyocytes,mediated by reduction in H3k4me3 levels through accumulatedα-ketoglutarate(αKG),and activation of the mitochondrial unfolded protein response(UPRmt),respectively.In this research highlight,we discuss the novel insights into mitochondrial-to-nuclear communication presented in these studies,the broad implications in cardiomyocyte biology and cardiovascular diseases,as well as the intriguing scientific questions inspired by the studies that may facilitate future investigations into the detailed molecular mechanisms of cardiomyo-cyte metabolism,proliferation,and mitochondrial-to-nuclear communications.
