4.8 Article

Resting mitochondrial complex I from Drosophila melanogaster adopts a helix-locked state

Journal

ELIFE
Volume 12, Issue -, Pages -

Publisher

eLIFE SCIENCES PUBL LTD
DOI: 10.7554/eLife.84415

Keywords

mitochondria; complex I; single particle cryoEM; electron transport chain; respiration

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Respiratory complex I plays a crucial role in bioenergetic metabolism and shows differences in behavior between Protostomia and Deuterostomia. The structure and conformational states of Drosophila melanogaster complex I provide insight into its functions and mechanisms in different organisms.
Respiratory complex I is a proton-pumping oxidoreductase key to bioenergetic metabolism. Biochemical studies have found a divide in the behavior of complex I in metazoans that aligns with the evolutionary split between Protostomia and Deuterostomia. Complex I from Deuterostomia including mammals can adopt a biochemically defined off-pathway 'deactive' state, whereas complex I from Protostomia cannot. The presence of off-pathway states complicates the interpretation of structural results and has led to considerable mechanistic debate. Here, we report the structure of mitochondrial complex I from the thoracic muscles of the model protostome Drosophila melanogaster. We show that although D. melanogaster complex I (Dm-CI) does not have a NEM-sensitive deactive state, it does show slow activation kinetics indicative of an off-pathway resting state. The resting-state structure of Dm-CI from the thoracic muscle reveals multiple conformations. We identify a helix-locked state in which an N-terminal a-helix on the NDUFS4 subunit wedges between the peripheral and membrane arms. Comparison of the Dm-CI structure and conformational states to those observed in bacteria, yeast, and mammals provides insight into the roles of subunits across organisms, explains why the Dm-CI off-pathway resting state is NEM insensitive, and raises questions regarding current mechanistic models of complex I turnover.

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