摘要Mammalian mitochondrial electron transport chain complexes are the most important and complicated protein machin-ery 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)struc-tures of porcine respiratory chain megacomplex-Ⅰ2Ⅲ2Ⅳ2(MCⅠ2Ⅲ2Ⅳ2)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 MCⅠ2Ⅲ2Ⅳ2 in live cells.Each MCⅠ2Ⅲ2Ⅳ2 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 CⅣ shown in the MCⅠ2Ⅲ2Ⅳ2 structure suggests this megacomplex could act as an integral unit in electron transfer and proton pumping.The conformational changes from different states sug-gest a plausible regulatory mechanism for the MCⅠ2Ⅲ2Ⅳ2 activation/deactivation process.