Human COX7A2L Regulates Complex III Biogenesis and Promotes Supercomplex Organization Remodeling without Affecting Mitochondrial Bioenergetics
Summary: 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,...
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doaj-fe2c9893ca9b4d149086a7d536dc5f1a2020-11-25T01:33:15ZengElsevierCell Reports2211-12472018-11-0125717861799.e4Human COX7A2L Regulates Complex III Biogenesis and Promotes Supercomplex Organization Remodeling without Affecting Mitochondrial BioenergeticsTeresa Lobo-Jarne0Eva Nývltová1Rafael Pérez-Pérez2Alba Timón-Gómez3Thibaut Molinié4Austin Choi5Arnaud Mourier6Flavia Fontanesi7Cristina Ugalde8Antoni Barrientos9Instituto de Investigación Hospital 12 de Octubre (i+12), 28041 Madrid, SpainDepartment of Neurology, University of Miami Miller School of Medicine, Miami, FL 33136, USAInstituto de Investigación Hospital 12 de Octubre (i+12), 28041 Madrid, SpainDepartment of Neurology, University of Miami Miller School of Medicine, Miami, FL 33136, USAUniversité de Bordeaux and Centre National de la Recherche Scientifique, Institut de Biochimie et Génétique Cellulaires UMR 5095, Bordeaux, FranceDepartment of Neurology, University of Miami Miller School of Medicine, Miami, FL 33136, USAUniversité de Bordeaux and Centre National de la Recherche Scientifique, Institut de Biochimie et Génétique Cellulaires UMR 5095, Bordeaux, FranceDepartment of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USAInstituto de Investigación Hospital 12 de Octubre (i+12), 28041 Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), U723, 28029 Madrid, Spain; Corresponding authorDepartment of Neurology, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Corresponding authorSummary: 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. : The role of COX7A2L in mitochondrial respiratory chain supercomplex biogenesis and function remains controversial. By analyzing COX7A2L-knockout human cells, Lobo-Jarne et al. report that this protein promotes specific respiratory chain complex assembly and organization remodeling but does not affect mitochondrial bioenergetics in physiological, nutritional, or oxidative stress conditions. Keywords: mitochondrial respiratory chain, supercomplexes, respirasomes, COX7A2L, COX7RP, complex III, SCAFIhttp://www.sciencedirect.com/science/article/pii/S2211124718316474 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Teresa Lobo-Jarne Eva Nývltová Rafael Pérez-Pérez Alba Timón-Gómez Thibaut Molinié Austin Choi Arnaud Mourier Flavia Fontanesi Cristina Ugalde Antoni Barrientos |
spellingShingle |
Teresa Lobo-Jarne Eva Nývltová Rafael Pérez-Pérez Alba Timón-Gómez Thibaut Molinié Austin Choi Arnaud Mourier Flavia Fontanesi Cristina Ugalde Antoni Barrientos Human COX7A2L Regulates Complex III Biogenesis and Promotes Supercomplex Organization Remodeling without Affecting Mitochondrial Bioenergetics Cell Reports |
author_facet |
Teresa Lobo-Jarne Eva Nývltová Rafael Pérez-Pérez Alba Timón-Gómez Thibaut Molinié Austin Choi Arnaud Mourier Flavia Fontanesi Cristina Ugalde Antoni Barrientos |
author_sort |
Teresa Lobo-Jarne |
title |
Human COX7A2L Regulates Complex III Biogenesis and Promotes Supercomplex Organization Remodeling without Affecting Mitochondrial Bioenergetics |
title_short |
Human COX7A2L Regulates Complex III Biogenesis and Promotes Supercomplex Organization Remodeling without Affecting Mitochondrial Bioenergetics |
title_full |
Human COX7A2L Regulates Complex III Biogenesis and Promotes Supercomplex Organization Remodeling without Affecting Mitochondrial Bioenergetics |
title_fullStr |
Human COX7A2L Regulates Complex III Biogenesis and Promotes Supercomplex Organization Remodeling without Affecting Mitochondrial Bioenergetics |
title_full_unstemmed |
Human COX7A2L Regulates Complex III Biogenesis and Promotes Supercomplex Organization Remodeling without Affecting Mitochondrial Bioenergetics |
title_sort |
human cox7a2l regulates complex iii biogenesis and promotes supercomplex organization remodeling without affecting mitochondrial bioenergetics |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2018-11-01 |
description |
Summary: 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. : The role of COX7A2L in mitochondrial respiratory chain supercomplex biogenesis and function remains controversial. By analyzing COX7A2L-knockout human cells, Lobo-Jarne et al. report that this protein promotes specific respiratory chain complex assembly and organization remodeling but does not affect mitochondrial bioenergetics in physiological, nutritional, or oxidative stress conditions. Keywords: mitochondrial respiratory chain, supercomplexes, respirasomes, COX7A2L, COX7RP, complex III, SCAFI |
url |
http://www.sciencedirect.com/science/article/pii/S2211124718316474 |
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