Mammalian mitochondrial electron transport chain complexes are the most important and complicated protein machinery in mitochondria.Although this system has been studied for more than a century,its composition and mol...Mammalian mitochondrial electron transport chain complexes are the most important and complicated protein machinery in mitochondria.Although this system has been studied for more than a century,its composition and molecular mechanism are still largely unknown.Here we report the high-resolution cryo-electron microscopy(Cryo-EM)structures of porcine respiratory chain megacomplex-Ⅰ_(2)Ⅲ_(2)Ⅳ_(2)(MCⅠ_(2)Ⅲ_(2)Ⅳ_(2))in five different conformations,including State 1,State 2,Mid 1,Mid 2,and Mid 3.High-resolution Cryo-EM imaging,combined with super-resolution gated stimulated emission depletion microscopy(gSTED),strongly supports the formation of MCⅠ_(2)Ⅲ_(2)Ⅳ_(2)in live cells.Each MCⅠ_(2)Ⅲ_(2)Ⅳ_(2)structure contains 141 subunits(70 different kinds of peptides,2.9 MDa)in total with 240 transmembrane helices.The mutual influence among CⅠ,CⅢ,and CⅣshown in the MCⅠ_(2)Ⅲ_(2)Ⅳ_(2)structure suggests this megacomplex could act as an integral unit in electron transfer and proton pumping.The conformational changes from different states suggest a plausible regulatory mechanism for the MCⅠ_(2)Ⅲ_(2)Ⅳ_(2)activation/deactivation process.展开更多
Dear Editor,Mitochondrial Ca2+homeostasis regulates energy production,cell division,and cell death.The basic properties of mitochondrial Ca2+uptake have been firmly established.The Ca2+influx is mediated by MCU,driven...Dear Editor,Mitochondrial Ca2+homeostasis regulates energy production,cell division,and cell death.The basic properties of mitochondrial Ca2+uptake have been firmly established.The Ca2+influx is mediated by MCU,driven by membrane potential and using a uniporter mechanism(Vasington and Murphy,1962).Patch-clamp analysis of MCU currents demonstrated that MCU is a channel with exceptionally high Ca2+selectivity(Kirichok et al.,2004).展开更多
基金supported by funds from the National Natural Science Foundation of China(32030056 and 32100962)the Tsinghua University Spring Breeze Fund(20201080572)+4 种基金the National Science Fund for Distinguished Young Scholars(3210110055)the China Postdoctoral Science Foundation(2020TQ0178,2020M680519,and 2020M680521)the Guangdong Basic and Applied Basic Research Foundation(2023B1515020039)the Shenzhen Science and Technology Program(RCYX20221008092904016)the Shenzhen University 2035 Program for Excellent Research(2022C012).
文摘Mammalian mitochondrial electron transport chain complexes are the most important and complicated protein machinery in mitochondria.Although this system has been studied for more than a century,its composition and molecular mechanism are still largely unknown.Here we report the high-resolution cryo-electron microscopy(Cryo-EM)structures of porcine respiratory chain megacomplex-Ⅰ_(2)Ⅲ_(2)Ⅳ_(2)(MCⅠ_(2)Ⅲ_(2)Ⅳ_(2))in five different conformations,including State 1,State 2,Mid 1,Mid 2,and Mid 3.High-resolution Cryo-EM imaging,combined with super-resolution gated stimulated emission depletion microscopy(gSTED),strongly supports the formation of MCⅠ_(2)Ⅲ_(2)Ⅳ_(2)in live cells.Each MCⅠ_(2)Ⅲ_(2)Ⅳ_(2)structure contains 141 subunits(70 different kinds of peptides,2.9 MDa)in total with 240 transmembrane helices.The mutual influence among CⅠ,CⅢ,and CⅣshown in the MCⅠ_(2)Ⅲ_(2)Ⅳ_(2)structure suggests this megacomplex could act as an integral unit in electron transfer and proton pumping.The conformational changes from different states suggest a plausible regulatory mechanism for the MCⅠ_(2)Ⅲ_(2)Ⅳ_(2)activation/deactivation process.
文摘Dear Editor,Mitochondrial Ca2+homeostasis regulates energy production,cell division,and cell death.The basic properties of mitochondrial Ca2+uptake have been firmly established.The Ca2+influx is mediated by MCU,driven by membrane potential and using a uniporter mechanism(Vasington and Murphy,1962).Patch-clamp analysis of MCU currents demonstrated that MCU is a channel with exceptionally high Ca2+selectivity(Kirichok et al.,2004).
