Aerobic metabolism is fundamental for almost all animal life. Cellular consumption of oxygen （O2） and production of carbon dioxide （CO2） signal metabolic states and physiologic stresses. These respiratory gases ar...Aerobic metabolism is fundamental for almost all animal life. Cellular consumption of oxygen （O2） and production of carbon dioxide （CO2） signal metabolic states and physiologic stresses. These respiratory gases are also detected as environmental cues that can signal external food quality and the presence of prey, predators and mates. In both contexts, animal nervous systems are endowed with mechanisms for sensing O2/CO2 to trigger appropriate behaviors and maintain homeostasis of internal O2/CO2. Although different animal species show different behavioral responses to O2/CO2, some underlying molecular mechanisms and pathways that function in the detection of respiratory gases are fundamentally similar and evolutionarily conserved. Studies of Caenorhabditis elegans and Drosophila melanogaster have identified roles for cyclic nucleotide signaling and the hypoxia inducible factor （HIF） transcriptional pathway in mediating behavioral responses to respiratory gases. Understanding how simple invertebrate nervous systems detect respiratory gases to control behavior might reveal general principles common to nematodes, insects and vertebrates that function in the molecular sensing of respiratory gases and the neural control of animal behaviors.展开更多
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
文摘Aerobic metabolism is fundamental for almost all animal life. Cellular consumption of oxygen （O2） and production of carbon dioxide （CO2） signal metabolic states and physiologic stresses. These respiratory gases are also detected as environmental cues that can signal external food quality and the presence of prey, predators and mates. In both contexts, animal nervous systems are endowed with mechanisms for sensing O2/CO2 to trigger appropriate behaviors and maintain homeostasis of internal O2/CO2. Although different animal species show different behavioral responses to O2/CO2, some underlying molecular mechanisms and pathways that function in the detection of respiratory gases are fundamentally similar and evolutionarily conserved. Studies of Caenorhabditis elegans and Drosophila melanogaster have identified roles for cyclic nucleotide signaling and the hypoxia inducible factor （HIF） transcriptional pathway in mediating behavioral responses to respiratory gases. Understanding how simple invertebrate nervous systems detect respiratory gases to control behavior might reveal general principles common to nematodes, insects and vertebrates that function in the molecular sensing of respiratory gases and the neural control of animal behaviors.
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.
