期刊
CELL REPORTS
卷 25, 期 7, 页码 1786-+出版社
CELL PRESS
DOI: 10.1016/j.celrep.2018.10.058
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资金
- NIH R01 [GM105781, GM112179]
- AHA Development Grant [14SDG20040003]
- Instituto de Salud Carlos III-MINECO/European FEDER Funds [PI14-00209, PI17-00048]
- AFM-Telethon [19613]
- ANR JCJC [ANR-16-CE14-0013]
- NIH R35 [GM118141]
- MDA Grant [MDA-381828]
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+IVn 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.
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