Cytochrome c Defects in Human Disease

Cytochrome c is a small soluble heme protein, encoded by the CYCS gene, which carries out several crucial functions in the cells. It is one of the two electron carriers in the mitochondrial respiratory chain, it is required for the mitochondrial importation of proteins with the CX3C and CX9C motifs through the MIA40/ERV1 pathway, it can both scavenge ROS or promote ROS production through p66shc, it catalyzes the oxidation of cardiolipin, and it is an essential player of the intrinsic pathway of apoptosis. Autosomal dominant mutations of CYCS have been reported in four families, and cause a peculiar clinical picture characterized by mild thrombocytopenia, with otherwise normal platelets, and none of the classical manifestations of respiratory chin defects. Functional and structural studies indicate that these mutations, cause a relatively minor respiratory defect, but increase the susceptibility to apoptosis in affected cells. The precise mechanism that links the proapoptotic effect to the abnormal platelet production is not completely clear.