CHCHD4 links AIF to the biogenesis of respiratory chain complex I

Abstract

During the evolution from yeast to mammals the Mia40 protein, the regulator of the redox-sensitive mitochondrial intermembrane space import machinery, has lost its membrane-anchorage segment to become CHCHD4, which interacts with the flavoprotein apoptosis-inducing factor (AIF). Our results establish CHCHD4 as the missing link between AIF deficiency and dysfunctional biogenesis of respiratory chain complexes.