Complexome Profiling—Exploring Mitochondrial Protein Complexes in Health and Disease
Por:
Cabrera-Orefice A., Potter A., Evers F., Hevler J.F., Guerrero-Castillo S.
Publicada:
1 ene 2022
Resumen:
Complexome profiling (CP) is a state-of-the-art approach that combines separation of native proteins by electrophoresis, size exclusion chromatography or density gradient centrifugation with tandem mass spectrometry identification and quantification. Resulting data are computationally clustered to visualize the inventory, abundance and arrangement of multiprotein complexes in a biological sample. Since its formal introduction a decade ago, this method has been mostly applied to explore not only the composition and abundance of mitochondrial oxidative phosphorylation (OXPHOS) complexes in several species but also to identify novel protein interactors involved in their assembly, maintenance and functions. Besides, complexome profiling has been utilized to study the dynamics of OXPHOS complexes, as well as the impact of an increasing number of mutations leading to mitochondrial disorders or rearrangements of the whole mitochondrial complexome. Here, we summarize the major findings obtained by this approach; emphasize its advantages and current limitations; discuss multiple examples on how this tool could be applied to further investigate pathophysiological mechanisms and comment on the latest advances and opportunity areas to keep developing this methodology. Copyright © 2022 Cabrera-Orefice, Potter, Evers, Hevler and Guerrero-Castillo.
Filiaciones:
Cabrera-Orefice A.:
Center for Molecular and Biomolecular Informatics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands
Potter A.:
Department of Pediatrics, Radboud Center for Mitochondrial Medicine, Radboud University Medical Center, Nijmegen, Netherlands
Evers F.:
Department of Medical Microbiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands
Hevler J.F.:
Biomolecular Mass Spectrometry and Proteomics, University of Utrecht, Utrecht, Netherlands
Bijvoet Center for Biomolecular Research, University of Utrecht, Utrecht, Netherlands
Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Utrecht, Netherlands
Netherlands Proteomics Center, Utrecht, Netherlands
Guerrero-Castillo S.:
University Children’s
Gold
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