Ablation of mitochondrial DNA results in widespread remodeling of the mitochondrial complexome

TY - JOUR

T1 - Ablation of mitochondrial DNA results in widespread remodeling of the mitochondrial complexome

AU - Guerrero-Castillo, Sergio

AU - van Strien, Joeri

AU - Brandt, Ulrich

AU - Arnold, Susanne

N1 - © 2021 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

PY - 2021/11/2

Y1 - 2021/11/2

N2 - So-called ρ0 cells lack mitochondrial DNA and are therefore incapable of aerobic ATP synthesis. How cells adapt to survive ablation of oxidative phosphorylation remains poorly understood. Complexome profiling analysis of ρ0 cells covered 1,002 mitochondrial proteins and revealed changes in abundance and organization of numerous multiprotein complexes including previously not described assemblies. Beyond multiple subassemblies of complexes that would normally contain components encoded by mitochondrial DNA, we observed widespread reorganization of the complexome. This included distinct changes in the expression pattern of adenine nucleotide carrier isoforms, other mitochondrial transporters, and components of the protein import machinery. Remarkably, ablation of mitochondrial DNA hardly affected the complexes organizing cristae junctions indicating that the altered cristae morphology in ρ0 mitochondria predominantly resulted from the loss of complex V dimers required to impose narrow curvatures to the inner membrane. Our data provide a comprehensive resource for in-depth analysis of remodeling of the mitochondrial complexome in response to respiratory deficiency.

AB - So-called ρ0 cells lack mitochondrial DNA and are therefore incapable of aerobic ATP synthesis. How cells adapt to survive ablation of oxidative phosphorylation remains poorly understood. Complexome profiling analysis of ρ0 cells covered 1,002 mitochondrial proteins and revealed changes in abundance and organization of numerous multiprotein complexes including previously not described assemblies. Beyond multiple subassemblies of complexes that would normally contain components encoded by mitochondrial DNA, we observed widespread reorganization of the complexome. This included distinct changes in the expression pattern of adenine nucleotide carrier isoforms, other mitochondrial transporters, and components of the protein import machinery. Remarkably, ablation of mitochondrial DNA hardly affected the complexes organizing cristae junctions indicating that the altered cristae morphology in ρ0 mitochondria predominantly resulted from the loss of complex V dimers required to impose narrow curvatures to the inner membrane. Our data provide a comprehensive resource for in-depth analysis of remodeling of the mitochondrial complexome in response to respiratory deficiency.

KW - Adaptation, Physiological

KW - Adenosine Triphosphate/metabolism

KW - Cell Line, Tumor

KW - DNA, Mitochondrial/genetics

KW - Gene Expression

KW - Humans

KW - Mitochondria/metabolism

KW - Mitochondrial Membranes/chemistry

KW - Mitochondrial Proteins/deficiency

KW - Multiprotein Complexes/deficiency

KW - Osteoblasts/metabolism

KW - Oxidative Phosphorylation

U2 - 10.15252/embj.2021108648

DO - 10.15252/embj.2021108648

M3 - SCORING: Journal article

C2 - 34542926

VL - 40

SP - e108648

JO - EMBO J

JF - EMBO J

SN - 0261-4189

IS - 21

ER -