7AK5

Cryo-EM structure of respiratory complex I in the deactive state from Mus musculus at 3.2 A

Summary for 7AK5

• Entry DOI: 10.2210/pdb7ak5/pdb
• EMDB information: 11810
• Descriptor: NADH-ubiquinone oxidoreductase chain 3, NADH-ubiquinone oxidoreductase chain 6, NADH-ubiquinone oxidoreductase chain 4L, ... (54 entities in total)
• Functional Keywords: deactive complex i, oxidoreductase
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 45
• Total formula weight: 1063250.64

Authors

Yin, Z.,Bridges, H.R.,Grba, D.,Hirst, J. (deposition date: 2020-09-29, release date: 2021-02-03, Last modification date: 2025-04-09)

Primary citation

Yin, Z.,Burger, N.,Kula-Alwar, D.,Aksentijevic, D.,Bridges, H.R.,Prag, H.A.,Grba, D.N.,Viscomi, C.,James, A.M.,Mottahedin, A.,Krieg, T.,Murphy, M.P.,Hirst, J.
Structural basis for a complex I mutation that blocks pathological ROS production.
Nat Commun, 12:707-707, 2021

PubMed Abstract: Mitochondrial complex I is central to the pathological reactive oxygen species (ROS) production that underlies cardiac ischemia-reperfusion (IR) injury. ND6-P25L mice are homoplasmic for a disease-causing mtDNA point mutation encoding the P25L substitution in the ND6 subunit of complex I. The cryo-EM structure of ND6-P25L complex I revealed subtle structural changes that facilitate rapid conversion to the "deactive" state, usually formed only after prolonged inactivity. Despite its tendency to adopt the "deactive" state, the mutant complex is fully active for NADH oxidation, but cannot generate ROS by reverse electron transfer (RET). ND6-P25L mitochondria function normally, except for their lack of RET ROS production, and ND6-P25L mice are protected against cardiac IR injury in vivo. Thus, this single point mutation in complex I, which does not affect oxidative phosphorylation but renders the complex unable to catalyse RET, demonstrates the pathological role of ROS production by RET during IR injury.

PubMed: 33514727
DOI: 10.1038/s41467-021-20942-w

Experimental method

ELECTRON MICROSCOPY (3.17 Å)