Format

Send to

Choose Destination
Mol Cell Proteomics. 2018 Feb;17(2):216-232. doi: 10.1074/mcp.RA117.000470. Epub 2017 Dec 8.

The interactome of intact mitochondria by cross-linking mass spectrometry provides evidence for coexisting respiratory supercomplexes.

Author information

1
From the ‡Biomolecular Mass Spectrometry and Proteomics. Bijvoet Centre for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Padualaan 8, 3584 CH, Utrecht, The Netherlands.
2
§Netherlands Proteomics Center, Padualaan 8, 3584 CH, Utrecht, The Netherlands.
3
¶Leibniz Institute of Molecular Pharmacology (FMP Berlin), Robert-Rössle-Straβe 10, 13125 Berlin, Germany.
4
‖Laboratory of Cardiac Energetics, Systems Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
5
‖Laboratory of Cardiac Energetics, Systems Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD balabanr@nhlbi.nih.gov a.j.r.heck@uu.nl.
6
From the ‡Biomolecular Mass Spectrometry and Proteomics. Bijvoet Centre for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Padualaan 8, 3584 CH, Utrecht, The Netherlands; balabanr@nhlbi.nih.gov a.j.r.heck@uu.nl.

Abstract

Mitochondria exert an immense amount of cytophysiological functions, but the structural basis of most of these processes is still poorly understood. Here we use cross-linking mass spectrometry to probe the organization of proteins in native mouse heart mitochondria. Our approach provides the largest survey of mitochondrial protein interactions reported so far. In total, we identify 3,322 unique residue-to-residue contacts involving half of the mitochondrial proteome detected by bottom-up proteomics. The obtained mitochondrial protein interactome gives insights in the architecture and submitochondrial localization of defined protein assemblies, and reveals the mitochondrial localization of four proteins not yet included in the MitoCarta database. As one of the highlights, we show that the oxidative phosphorylation complexes I-V exist in close spatial proximity, providing direct evidence for supercomplex assembly in intact mitochondria. The specificity of these contacts is demonstrated by comparative analysis of mitochondria after high salt treatment, which disrupts the native supercomplexes and substantially changes the mitochondrial interactome.

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center