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

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15 Citations (Scopus)


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. 

Original languageEnglish
Article numbere2019665118
Number of pages9
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number17
Publication statusPublished - 27 Apr 2021


  • Complex I
  • Membrane protein
  • Mitochondria
  • Optic atrophy
  • Oxidative phosphorylation

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