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Cryo-EM structures of complex I from mouse heart mitochondria in two biochemically defined states

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Agip, Ahmed-Noor A., Blaza, James N., Bridges, Hannah R., Viscomi, Carlo, Rawson, Shaun, Muench, Stephen P., Hirst, Judy·2018·Nature Structural & Molecular Biology

Abstract

Complex I (NADH:ubiquinone oxidoreductase) uses the reducing potential of NADH to drive protons across the energy-transducing inner membrane and power oxidative phosphorylation in mammalian mitochondria. Recent cryo-EM analyses have produced near-complete models of all 45 subunits in the bovine, ovine and porcine complexes and have identified two states relevant to complex I in ischemia–reperfusion injury. Here, we describe the 3.3-Å structure of complex I from mouse heart mitochondria, a biomedically relevant model system, in the ‘active’ state. We reveal a nucleotide bound in subunit NDUFA10, a nucleoside kinase homolog, and define mechanistically critical elements in the mammalian enzyme. By comparisons with a 3.9-Å structure of the ‘deactive’ state and with known bacterial structures, we identify differences in helical geometry in the membrane domain that occur upon activation or that alter the positions of catalytically important charged residues. Our results demonstrate the capability of cryo-EM analyses to challenge and develop mechanistic models for mammalian complex I. Cryo-EM analyses of mitochondrial complex I (NADH:ubiquinone oxidoreductase) isolated from mouse heart allow comparisons between the active and deactive states and provide new mechanistic insights into this important complex.

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Metadata

Authors
Agip, A.-N. A., Blaza, J. N., Bridges, H. R., Viscomi, C., Rawson, S., Muench, S. P., & Hirst, J.
Venue
Nature Structural & Molecular Biology
Published
2018-06-18
Volume
25
Issue
7
Pages
548-556
ISSN
  • 1545-9985 (ISSN-L)
  • 1545-9993
OpenAlex
W2806917274
Cited by
228
References
6
FWCI
10.12
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Cryo-EM structures of complex I from mouse heart mitochondria in two biochemically defined states. https://app.cochat.ai/papers/10.1038/s41594-018-0073-1
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Agip, A.-N. A., Blaza, J. N., Bridges, H. R., Viscomi, C., Rawson, S., Muench, S. P., & Hirst, J. (2018). Cryo-EM structures of complex I from mouse heart mitochondria in two biochemically defined states. Nature Structural & Molecular Biology. https://doi.org/10.1038/s41594-018-0073-1

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