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Lobo-Jarne 2018 Cell Rep

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Publications in the MiPMap
Lobo-Jarne T, Nývltová E, Pérez-Pérez R, Timón-Gómez A, Molinié T, Choi A, Mourier A, Fontanesi F, Ugalde C, Barrientos A (2018) Human COX7A2L regulates complex III biogenesis and promotes supercomplex organization remodeling without affecting mitochondrial bioenergetics. Cell Rep 25:1786-99.

» PMID: 30428348 Open Access

Lobo-Jarne T, Nyvltova E, Perez-Perez R, Timon-Gomez A, Molinie T, Choi A, Mourier A, Fontanesi F, Ugalde C, Barrientos A (2018) Cell Rep

Abstract: 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. Keywords: COX7A2L, COX7RP, SCAFI, Complex III, Mitochondrial respiratory chain, Respirasomes, Supercomplexes, Human glioblastoma U87 cells Bioblast editor: Plangger M O2k-Network Lab: US FL Miami Barrientos A


Labels: MiParea: Respiration, Genetic knockout;overexpression 


Organism: Human  Tissue;cell: Other cell lines, HEK  Preparation: Permeabilized cells  Enzyme: Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Supercomplex 

Coupling state: LEAK, OXPHOS, ET  Pathway: N, S, Gp, NS, ROX  HRR: Oxygraph-2k 

2018-12