Complexome Profiling-Exploring Mitochondrial Protein Complexes in Health and Disease

TY - JOUR

T1 - Complexome Profiling-Exploring Mitochondrial Protein Complexes in Health and Disease

AU - Cabrera-Orefice, Alfredo

AU - Potter, Alisa

AU - Evers, Felix

AU - Hevler, Johannes F

AU - Guerrero-Castillo, Sergio

N1 - Copyright © 2022 Cabrera-Orefice, Potter, Evers, Hevler and Guerrero-Castillo.

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

U2 - 10.3389/fcell.2021.796128

DO - 10.3389/fcell.2021.796128

M3 - SCORING: Review article

C2 - 35096826

VL - 9

SP - 796128

JO - FRONT CELL DEV BIOL

JF - FRONT CELL DEV BIOL

SN - 2296-634X

ER -