Open AccessOptic atrophy–associated TMEM126A is an assembly factor for the ND4-module of mitochondrial complex I
Author(s) -
Luke E. Formosa,
Boris Reljić,
Alice J. Sharpe,
Daniella H Hock,
Linden Muellner-Wong,
David A. Stroud,
Michael Ryan
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2019665118
Subject(s) - mitochondrial dna , protein subunit , biology , mitochondrion , genetics , mutation , microbiology and biotechnology , gene
Significance Mitochondria are critical organelles that play a central role in energy conversion in cells. Mutations in genes encoding mitochondrial proteins can lead to disease. Here, we discover that the optic atrophy–associated mitochondrial disease gene TMEM126A plays a role in the assembly of the first enzyme of the respiratory chain, complex I. Critically, we show that TMEM126A interacts in a complex with newly synthesized ND4, a highly hydrophobic subunit of complex I that is encoded by mitochondrial DNA. Our findings expand the molecular machinery required to build complex I from its constituent subunits and elucidates the function of a gene mutated in mitochondrial disease.