Two mitochondrial DNA polymorphisms modulate cardiolipin binding and lead to synthetic lethality.

ABSTRACT: Genetic screens have been used extensively to probe interactions between nuclear genes and their impact on phenotypes. Probing interactions between mitochondrial genes and their phenotypic outcome, however, has not been possible due to a lack of tools to map the responsible polymorphisms. Here, using a toolkit we previously established in Drosophila, we isolate over 300 recombinant mitochondrial genomes and map a naturally occurring polymorphism at the cytochrome c oxidase III residue 109 (CoIII¹⁰⁹) that fully rescues the lethality and other defects associated with a point mutation in cytochrome c oxidase I (CoI^T300I). Through lipidomics profiling, biochemical assays and phenotypic analyses, we show that the CoIII¹⁰⁹ polymorphism modulates cardiolipin bindi

SUBMITTER: Chiang ACY 

PROVIDER: S-EPMC10799063 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature