Mitochondrial complex III Rieske Fe-S protein processing and assembly.

Regulation of the mitochondrial respiratory chain biogenesis is a matter of great interest because of its implications for mitochondrial disease. One of the mitochondrial disease genes recently discovered associated to encephalopathy and mitochondrial complex III (cIII) deficiency is TTC19. Our study of TTC19-deficient human and mouse models, has led us to propose a post-assembly quality control role or 'husbandry' function for this factor that is linked to Rieske Fe-S protein (UQCRFS1). UQCRFS1 is the last incorporated cIII subunit, and its presence is essential for enzymatic activity. During UQCRFS1 assembly, the precursor is cleaved and its N-terminal part remains bound to the complex, between the two core subunits (UQCRC1 and UQCRC2). In the absence of TTC19 there is a prominent accumulation of these UQCRFS1-derived N-terminal fragments that proved to be detrimental for cIII function. In this article we will discuss some ideas around the UQCRFS1 processing and assembly and its importance for the regulation of cIII activity and biogenesis.