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Human COX7A2L Regulates Complex III Biogenesis and Promotes Supercomplex Organization Remodeling without Affecting Mitochondrial Bioenergetics.

Cell reports | 2018

The mitochondrial respiratory chain is organized in a dynamic set of supercomplexes (SCs). The COX7A2L protein is essential for mammalian SC III2+IV assembly. However, its function in respirasome (SCs I+III2+IVn) biogenesis remains controversial. To unambiguously determine the COX7A2L role, we generated COX7A2L-knockout (COX7A2L-KO) HEK293T and U87 cells. COX7A2L-KO cells lack SC III2+IV but have enhanced complex III steady-state levels, activity, and assembly rate, normal de novo complex IV biogenesis, and delayed respirasome formation. Nonetheless, the KOs have normal respirasome steady-state levels, and only larger structures (SCs I1-2+III2+IV2-n or megacomplexes) were undetected. Functional substrate-driven competition assays showed normal mitochondrial respiration in COX7A2L-KO cells in standard and nutritional-, environmental-, and oxidative-stress-challenging conditions. We conclude that COX7A2L establishes a regulatory checkpoint for the biogenesis of CIII2 and specific SCs, but the COX7A2L-dependent MRC remodeling is essential neither to maintain mitochondrial bioenergetics nor to cope with acute cellular stresses.

Pubmed ID: 30428348 RIS Download

Research resources used in this publication

Antibodies used in this publication

Associated grants

  • Agency: BLRD VA, United States
    Id: I01 BX003303
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM105781
  • Agency: NIGMS NIH HHS, United States
    Id: R35 GM118141

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This is a list of tools and resources that we have found mentioned in this publication.


SPSS (tool)

RRID:SCR_002865

Software package used for interactive, or batched, statistical analysis in social science, health sciences and marketing. Software platform offers advanced statistical analysis, a library of machine-learning algorithms, text analysis, open-source extensibility, integration with big data and deployment into applications.Versions that were produced by SPSS Inc. before the IBM acquisition (Versions 18 and earlier) would be given origin or publisher of SPSS Inc. in Chicago.

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GeneCopoeia (tool)

RRID:SCR_003145

Commercial organization which provides reagents and services for molecular biology research. Its services include clone collections, microRNA solutions, genome editing, qPCR products, and fluorescent labeling and detection.

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ATCC (tool)

RRID:SCR_001672

Global nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.

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Promega (tool)

RRID:SCR_006724

An Antibody supplier

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Molecular Probes (tool)

RRID:SCR_013318

An Antibody supplier and subset of ThermoFisher Scientific which provides fluorescence reagents for various experiments and methods.

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HEK293T (tool)

RRID:CVCL_0063

Cell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)

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HEK293 (tool)

RRID:CVCL_0045

Cell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)

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U-87MG ATCC (tool)

RRID:CVCL_0022

Cell line U-87MG ATCC is a Cancer cell line with a species of origin Homo sapiens (Human)

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Ubiquinol-Cytochrome C Reductase Core Protein I antibody [16D10AD9AH5] (antibody)

RRID:AB_10863633

This monoclonal targets Ubiquinol-Cytochrome C Reductase Core Protein I antibody [16D10AD9AH5]

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Tom20 (FL-145) Antibody (antibody)

RRID:AB_2207533

This polyclonal targets Tom20 (FL-145)

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COXIV Isoform 2 antibody (antibody)

RRID:AB_2085283

This polyclonal targets COX4I2

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BCS1L antibody (antibody)

RRID:AB_10859410

This polyclonal targets BCS1L antibody

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TIMM50 antibody [EPR5784] (antibody)

RRID:AB_10858241

This monoclonal targets TIMM50 antibody [EPR5784]

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Anti-COX6A1 polyclonal antibody (antibody)

RRID:AB_2684749

This polyclonal targets COX6A1

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COX6A2 antibody (antibody)

RRID:AB_10710958

This polyclonal targets COX6A2 antibody

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Anti-SOD2 antibody produced in rabbit (antibody)

RRID:AB_1080134

This polyclonal targets SOD2 antibody produced in rabbit

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COX7A2L antibody (antibody)

RRID:AB_2245402

This polyclonal targets COX7A2L

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UQCRC2 antibody [13G12] (antibody)

RRID:AB_2213640

This monoclonal targets Uqcrc2

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Ndufs1 antibody (antibody)

RRID:AB_2151096

This polyclonal targets Ndufs1 antibody

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Cytochrome C oxidase subunit II antibody [12C4F12 ] (antibody)

RRID:AB_10887758

This monoclonal targets Cytochrome C oxidase subunit II antibody [12C4F12 ]

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Monoclonal Anti-beta-Tubulin-Cy3 antibody produced in mouse (antibody)

RRID:AB_258868

This monoclonal targets beta-Tubulin-Cy3 antibody produced in mouse

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Anti-RABBIT IgG (H&L) (GOAT) Antibody Peroxidase Conjugated - 611-1302 (antibody)

RRID:AB_219720

This unknown targets RABBIT IgG (H&L) Secondary Antibody Peroxidase Conjugated

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beta Actin antibody - Loading Control (antibody)

RRID:AB_2305186

This polyclonal targets RCJMB04_4h19

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COX5b (B-2) (antibody)

RRID:AB_10988066

This monoclonal targets COX5b (B-2)

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COX7A2L antibody (antibody)

RRID:AB_2245402

This polyclonal targets COX7A2L

View all literature mentions

Tom20 (FL-145) Antibody (antibody)

RRID:AB_2207533

This polyclonal targets Tom20 (FL-145)

View all literature mentions

Anti-RABBIT IgG (H&L) (GOAT) Antibody Peroxidase Conjugated - 611-1302 (antibody)

RRID:AB_219720

This unknown targets RABBIT IgG (H&L) Secondary Antibody Peroxidase Conjugated

View all literature mentions

UQCRC2 antibody [13G12] (antibody)

RRID:AB_2213640

This monoclonal targets Uqcrc2

View all literature mentions

BCS1L antibody (antibody)

RRID:AB_10859410

This polyclonal targets BCS1L antibody

View all literature mentions

Cytochrome C oxidase subunit II antibody [12C4F12 ] (antibody)

RRID:AB_10887758

This monoclonal targets Cytochrome C oxidase subunit II antibody [12C4F12 ]

View all literature mentions

Ubiquinol-Cytochrome C Reductase Core Protein I antibody [16D10AD9AH5] (antibody)

RRID:AB_10863633

This monoclonal targets Ubiquinol-Cytochrome C Reductase Core Protein I antibody [16D10AD9AH5]

View all literature mentions

Anti-COX6A1 polyclonal antibody (antibody)

RRID:AB_2684749

This polyclonal targets COX6A1

View all literature mentions

beta Actin antibody - Loading Control (antibody)

RRID:AB_2305186

This polyclonal targets RCJMB04_4h19

View all literature mentions

Anti-SOD2 antibody produced in rabbit (antibody)

RRID:AB_1080134

This polyclonal targets SOD2 antibody produced in rabbit

View all literature mentions

Monoclonal Anti-beta-Tubulin-Cy3 antibody produced in mouse (antibody)

RRID:AB_258868

This monoclonal targets beta-Tubulin-Cy3 antibody produced in mouse

View all literature mentions

COXIV Isoform 2 antibody (antibody)

RRID:AB_2085283

This polyclonal targets COX4I2

View all literature mentions

COX6A2 antibody (antibody)

RRID:AB_10710958

This polyclonal targets COX6A2 antibody

View all literature mentions

TIMM50 antibody [EPR5784] (antibody)

RRID:AB_10858241

This monoclonal targets TIMM50 antibody [EPR5784]

View all literature mentions

COX5b (B-2) (antibody)

RRID:AB_10988066

This monoclonal targets COX5b (B-2)

View all literature mentions

Ndufs1 antibody (antibody)

RRID:AB_2151096

This polyclonal targets Ndufs1 antibody

View all literature mentions

Monoclonal Anti-beta-Tubulin-Cy3 antibody produced in mouse (antibody)

RRID:AB_258868

This monoclonal targets beta-Tubulin-Cy3 antibody produced in mouse

View all literature mentions

Ubiquinol-Cytochrome C Reductase Core Protein I antibody [16D10AD9AH5] (antibody)

RRID:AB_10863633

This monoclonal targets Ubiquinol-Cytochrome C Reductase Core Protein I antibody [16D10AD9AH5]

View all literature mentions

beta Actin antibody - Loading Control (antibody)

RRID:AB_2305186

This polyclonal targets RCJMB04_4h19

View all literature mentions

Anti-RABBIT IgG (H&L) (GOAT) Antibody Peroxidase Conjugated - 611-1302 (antibody)

RRID:AB_219720

This unknown targets RABBIT IgG (H&L) Secondary Antibody Peroxidase Conjugated

View all literature mentions

Anti-SOD2 antibody produced in rabbit (antibody)

RRID:AB_1080134

This polyclonal targets SOD2 antibody produced in rabbit

View all literature mentions

Tom20 (FL-145) Antibody (antibody)

RRID:AB_2207533

This polyclonal targets Tom20 (FL-145)

View all literature mentions

TIMM50 antibody [EPR5784] (antibody)

RRID:AB_10858241

This monoclonal targets TIMM50 antibody [EPR5784]

View all literature mentions

Ndufs1 antibody (antibody)

RRID:AB_2151096

This polyclonal targets Ndufs1 antibody

View all literature mentions

Anti-COX6A1 polyclonal antibody (antibody)

RRID:AB_2684749

This polyclonal targets COX6A1

View all literature mentions

COX7A2L antibody (antibody)

RRID:AB_2245402

This polyclonal targets COX7A2L

View all literature mentions

COX6A2 antibody (antibody)

RRID:AB_10710958

This polyclonal targets COX6A2 antibody

View all literature mentions

COX5b (B-2) (antibody)

RRID:AB_10988066

This monoclonal targets COX5b (B-2)

View all literature mentions

Cytochrome C oxidase subunit II antibody [12C4F12 ] (antibody)

RRID:AB_10887758

This monoclonal targets Cytochrome C oxidase subunit II antibody [12C4F12 ]

View all literature mentions

COXIV Isoform 2 antibody (antibody)

RRID:AB_2085283

This polyclonal targets COX4I2

View all literature mentions

UQCRC2 antibody [13G12] (antibody)

RRID:AB_2213640

This monoclonal targets Uqcrc2

View all literature mentions

BCS1L antibody (antibody)

RRID:AB_10859410

This polyclonal targets BCS1L antibody

View all literature mentions