WAH-1/AIF regulates mitochondrial oxidative phosphorylation in the nematode Caenorhabditis elegans

Abstract

Impaired mitochondrial energy metabolism contributes to a wide range of pathologic conditions, including neurodegenerative diseases. Mitochondrial apoptosis-inducing factor (AIF) is required for the correct maintenance of mitochondrial electron transport chain. An emerging body of clinical evidence indicates that several mutations in the <i>AIFM1</i> gene are causally linked to severe forms of mitochondrial disorders. Here we investigate the consequence of WAH-1/AIF deficiency in the survival of the nematode <i>Caenorhabditis elegans</i>. Moreover, we assess the survival of <i>C</i>. <i>elegans</i> strains expressing a disease-associated WAH-1/AIF variant. We demonstrate that <i>wah-1</i> downregulation compromises the function of the oxidative phosphorylation system and reduces <i>C</i>. <i>elegans</i> lifespan. Notably, the loss of respiratory subunits induces a nuclear-encoded mitochondrial stress response independently of an evident increase of oxidative stress. Overall, our data pinpoint an evolutionarily conserved role of WAH-1/AIF in the maintenance of proper mitochondrial activity.