Optic atrophy-associated TMEM126A is an assembly factor for the ND4-module of mitochondrial complex I.

Luke E Formosa, Boris Reljic, Alice J Sharpe, Daniella H Hock, Linden Muellner-Wong, David A Stroud, Michael T Ryan

Proceedings of the National Academy of Sciences of the United States of America 2021 Apr 27

filter terms:

Mitochondrial disease is a debilitating condition with a diverse genetic etiology. Here, we report that TMEM126A, a protein that is mutated in patients with autosomal-recessive optic atrophy, participates directly in the assembly of mitochondrial complex I. Using a combination of genome editing, interaction studies, and quantitative proteomics, we find that loss of TMEM126A results in an isolated complex I deficiency and that TMEM126A interacts with a number of complex I subunits and assembly factors. Pulse-labeling interaction studies reveal that TMEM126A associates with the newly synthesized mitochondrial DNA (mtDNA)-encoded ND4 subunit of complex I. Our findings indicate that TMEM126A is involved in the assembly of the ND4 distal membrane module of complex I. In addition, we find that the function of TMEM126A is distinct from its paralogue TMEM126B, which acts in assembly of the ND2-module of complex I.

Citation

Luke E Formosa, Boris Reljic, Alice J Sharpe, Daniella H Hock, Linden Muellner-Wong, David A Stroud, Michael T Ryan. Optic atrophy-associated TMEM126A is an assembly factor for the ND4-module of mitochondrial complex I. Proceedings of the National Academy of Sciences of the United States of America. 2021 Apr 27;118(17)