Hevler, Johannes F., Chiozzi, Riccardo Zenezeni, Cabrera-Orefice, Alfredo ORCID: 0000-0002-2042-3794, Brandt, Ulrich ORCID: 0000-0003-1869-6811, Arnold, Susanne ORCID: 0000-0003-2667-5156 and Heck, Albert J. R. (2021). Molecular characterization of a complex of apoptosis-inducing factor 1 with cytochrome c oxidase of the mitochondrial respiratory chain. Proc. Natl. Acad. Sci. U. S. A., 118 (39). WASHINGTON: NATL ACAD SCIENCES. ISSN 0027-8424

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Abstract

Combining mass spectrometry-based chemical cross-linking and complexome profiling, we analyzed the interactome of heart mitochondria. We focused on complexes of oxidative phosphorylation and found that dimeric apoptosis-inducing factor 1 (AIFM1) forms a defined complex with similar to 10% of monomeric cytochrome c oxidase (COX) but hardly interacts with respiratory chain supercomplexes. Multiple AIFM1 intercross-links engaging six different COX subunits provided structural restraints to build a detailed atomic model of the COX-AIFM1(2) complex (PDBDEV_00000092). An application of two complementary proteomic approaches thus provided unexpected insight into the macromolecular organization of the mitochondrial complexome. Our structural model excludes direct electron transfer between AIFM1 and COX. Notably, however, the binding site of cytochrome c remains accessible, allowing formation of a ternary complex. The discovery of the previously overlooked COX-AIFM12 complex and clues provided by the structural model hint at potential roles of AIFM1 in oxidative phosphorylation biogenesis and in programmed cell death.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Hevler, Johannes F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chiozzi, Riccardo ZenezeniUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cabrera-Orefice, AlfredoUNSPECIFIEDorcid.org/0000-0002-2042-3794UNSPECIFIED
Brandt, UlrichUNSPECIFIEDorcid.org/0000-0003-1869-6811UNSPECIFIED
Arnold, SusanneUNSPECIFIEDorcid.org/0000-0003-2667-5156UNSPECIFIED
Heck, Albert J. R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-580414
DOI: 10.1073/pnas.2106950118
Journal or Publication Title: Proc. Natl. Acad. Sci. U. S. A.
Volume: 118
Number: 39
Date: 2021
Publisher: NATL ACAD SCIENCES
Place of Publication: WASHINGTON
ISSN: 0027-8424
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
WEB SERVER; OXIDATIVE-PHOSPHORYLATION; PROTEIN INTERACTIONS; UCSF CHIMERA; FACTOR AIF; INTERACTOME; AFFINITY; DATABASE; KINETICS; DIMERMultiple languages
Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/58041

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