4.5 Article

Structure of respiratory complex I - An emerging blueprint for the mechanism

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CURRENT BIOLOGY LTD
DOI: 10.1016/j.sbi.2022.102350

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In this review, the importance, structure, and mechanisms of complex I in respiratory processes are discussed. By comparing structural evidence and mutagenesis data from different species, the mechanisms of electron transfer and proton pumping are elucidated, and the structural basis of deactivation phenomenon in complex I is explained.
Complex I is one of the major respiratory complexes, conserved from bacteria to mammals. It oxidises NADH, reduces quinone and pumps protons across the membrane, thus playing a central role in the oxidative energy metabolism. In this review we discuss our current state of understanding the structure of complex I from various species of mammals, plants, fungi, and bacteria, as well as of several complex I-related proteins. By comparing the structural evidence from these systems in different redox states and data from mutagenesis and molecular simulations, we formulate the mechanisms of electron transfer and proton pumping and explain how they are conformationally and electrostatically coupled. Finally, we discuss the structural basis of the deactivation phenomenon in mammalian complex I.

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