Dear Editor, Mitochondrial complex I is important for cellular ATP producti on by tran sporti ng electro ns and gen erati ng proton gradient across the mitochondrial inner membrane (Hirst, 2013). It is also a major ce...Dear Editor, Mitochondrial complex I is important for cellular ATP producti on by tran sporti ng electro ns and gen erati ng proton gradient across the mitochondrial inner membrane (Hirst, 2013). It is also a major cellular locus where electron leakage to oxygen produces superoxide, an ROS (reactive oxygen species), particularly under oxidative stress conditions. Dysfunctional complex I contributes to the most comm on oxidative phosphorylation disorder in humans, with many iden tified gen etic mutati ons in complex I sub units causing a variety of human disorders including Leigh syndrome, encephalomyopathy, cardiomyopathy, parkinsonism and hereditary optic neuropathy (Hirst, 2013;Guo et al., 2017). In addition, complex I is the major target of many parkinsonismcausing neurotoxins including rotenone and MPTP. Past biochemical, cell biological and structural studies have elucidated how complex I functions normally in mitochondrial respiration (Hirst, 2013;Guo et al., 2017;Letts and Sazanov, 2017). Nonetheless, our understanding of mechanisms how complex I dysfunction leads to human diseases is far from completion;therapeutic targets and strategies are urgently needed.展开更多
Cardiac regeneration is an ancestral trait in vertebrates that is lost both as more recent vertebrate lineages evolved to adapt to new environments and selective pressures,and as members of certain species development...Cardiac regeneration is an ancestral trait in vertebrates that is lost both as more recent vertebrate lineages evolved to adapt to new environments and selective pressures,and as members of certain species developmentally progress towards their adult forms.While higher vertebrates like humans and rodents resolve cardiac injury with permanent fibrosis and loss of cardiac output as adults,neonates of these same species can fully regenerate heart structure and function after injury–as can adult lower vertebrates like many teleost fish and urodele amphibians.Recent research has elucidated several broad factors hypothesized to contribute to this loss of cardiac regenerative potential both evolutionarily and developmentally:an oxygen-rich environment,vertebrate thermogenesis,a complex adaptive immune system,and cancer risk trade-offs.In this review,we discuss the evidence for these hypotheses as well as the cellular participators and molecular regulators by which they act to govern heart regeneration in vertebrates.展开更多
文摘Dear Editor, Mitochondrial complex I is important for cellular ATP producti on by tran sporti ng electro ns and gen erati ng proton gradient across the mitochondrial inner membrane (Hirst, 2013). It is also a major cellular locus where electron leakage to oxygen produces superoxide, an ROS (reactive oxygen species), particularly under oxidative stress conditions. Dysfunctional complex I contributes to the most comm on oxidative phosphorylation disorder in humans, with many iden tified gen etic mutati ons in complex I sub units causing a variety of human disorders including Leigh syndrome, encephalomyopathy, cardiomyopathy, parkinsonism and hereditary optic neuropathy (Hirst, 2013;Guo et al., 2017). In addition, complex I is the major target of many parkinsonismcausing neurotoxins including rotenone and MPTP. Past biochemical, cell biological and structural studies have elucidated how complex I functions normally in mitochondrial respiration (Hirst, 2013;Guo et al., 2017;Letts and Sazanov, 2017). Nonetheless, our understanding of mechanisms how complex I dysfunction leads to human diseases is far from completion;therapeutic targets and strategies are urgently needed.
基金This research was made possible by NIH F31 Fellowship(S.C.),NIH(R01HL138456)Department of Defense(W81XWH1910206)Program for Breakthrough Biomedical Research,and UCSF Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research Seed Grant(G.N.H.).
文摘Cardiac regeneration is an ancestral trait in vertebrates that is lost both as more recent vertebrate lineages evolved to adapt to new environments and selective pressures,and as members of certain species developmentally progress towards their adult forms.While higher vertebrates like humans and rodents resolve cardiac injury with permanent fibrosis and loss of cardiac output as adults,neonates of these same species can fully regenerate heart structure and function after injury–as can adult lower vertebrates like many teleost fish and urodele amphibians.Recent research has elucidated several broad factors hypothesized to contribute to this loss of cardiac regenerative potential both evolutionarily and developmentally:an oxygen-rich environment,vertebrate thermogenesis,a complex adaptive immune system,and cancer risk trade-offs.In this review,we discuss the evidence for these hypotheses as well as the cellular participators and molecular regulators by which they act to govern heart regeneration in vertebrates.
