蛋白质亚单位
细胞色素c氧化酶
线粒体
化学
生物
突变
电子传递复合物IV
生物化学
细胞生物学
HEK 293细胞
氧化酶试验
分子生物学
基因
突变
酶
作者
Daria Rotko,Alexei P. Kudin,Gábor Zsurka,Bogusz Kulawiak,Adam Szewczyk,Wolfram S. Kunz
出处
期刊:Biokhimiya
[Springer Nature]
日期:2021-01-01
卷期号:86 (1): 33-43
被引量:2
标识
DOI:10.1134/s0006297921010041
摘要
In this work we studied molecular and functional effects of the loss of the smallest nuclear encoded subunit of cytochrome c oxidase COX8A in fibroblasts from a patient with a homozygous splice site mutation and in CRISPR/Cas9 genome-edited HEK293T cells. In both cellular model systems, between 20 to 30% of the residual enzymatic activity of cytochrome c oxidase (COX) was detectable. In immunoblots of BN-PAGE separated mitochondria from both cellular models almost no monomers and dimers of the fully assembled COX could be visualized. Interestingly, supercomplexes of COX formed with complex III and also with complexes I and III retained considerable immunoreactivity, while nearly no immunoreactivity attributable to subassemblies was found. That indicates that COX lacking subunit 8A is stabilized in supercomplexes, while monomers and dimers are rapidly degraded. With transcriptome analysis by 3'-RNA sequencing we failed to detect in our cellular models of COX8A deficiency transcriptional changes of genes involved in the mitochondrial unfolded protein response (mtUPR) and the integrated stress response (ISR). Thus, our data strongly suggest that the smallest subunit of cytochrome c oxidase COX8A is required for maintenance of the structural stability of COX monomers and dimers.
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