Fig. 6.

A model for the function of CISD3 in mitochondria from skeletal muscles of mice. CISD3 is shown to donate its [2Fe-2S] clusters to NDUFV2 (and perhaps other 2Fe-2S proteins of complexes I and II), thereby supporting the function of the mitochondrial respiratory chain in muscle mitochondria and enabling enhanced metabolic activity. Based on previous studies in cancer cells (22, 23), CISD3 is also proposed to function as a part of a [2Fe-2S] cluster relay that transfer clusters from within the mitochondria to the cytosol. In the absence of CISD3 the function of the mitochondrial respiratory chain is reduced, and mitochondria are more prone to iron overload and structural damage. Abbreviations: CISD, CDGSH Iron Sulfur Domain; NDUFV2, NADH:ubiquinone oxidoreductase core subunit V2; OXPHOS, oxidative phosphorylation; ROS, reactive oxygen species.