Molecular characterization of a complex of apoptosis-inducing factor 1 with cytochrome c oxidase of the mitochondrial respiratory chain
Por:
Hevler J.F., Chiozzi R.Z., Cabrera-Orefice A., Brandt U., Arnold S., Heck A.J.R.
Publicada:
1 ene 2021
Categoría:
Multidisciplinary
Resumen:
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 ~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 COXAIFM12 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. © 2021 National Academy of Sciences. All rights reserved.
Filiaciones:
Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research, Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Utrecht, 3584 CH, Netherlands
Netherlands Proteomics Center, Bijvoet Center for Biomolecular Research, Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Utrecht, 3584 CH, Netherlands
Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, 6525 GA, Netherlands
Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, 50931, Germany
All Open Access; Green
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