THE SACCHAROMYCES-CEREVISIAE TCM62 GENE ENCODES A CHAPERONE NECESSARYFOR THE ASSEMBLY OF THE MITOCHONDRIAL SUCCINATE-DEHYDROGENASE (COMPLEX-II)

The assembly of the mitochondrial respiratory chain is mediated by a l arge number of helper proteins. To better understand the biogenesis of the yeast succinate dehydrogenase (SDH), we searched for assembly-def ective mutants. SDH is encoded by the SDR1, SDH2, SDH3, and SDH4 genes . The holoenzyme is composed of two domains. The membrane extrinsic do main, consisting of Sdh1p and Sdh2p, contains a covalent FAD cofactor and three iron-sulfur clusters. The membrane intrinsic domain, consist ing of Sdh3p and Sdh4p, is proposed to bind two molecules of ubiquinon e and one heme. me isolated one mutant that is respiration-deficient w ith a specific loss of SDH oxidase activity. SDH is not assembled in t his mutant. The complementing gene, TCM62 (also known as SCYBR044C), d oes not encode an SDH subunit and is not essential for cell viability. It encodes a mitochondrial membrane protein of 64,211 Da. The Tcm62p sequence is 17.3% identical to yeast hsp80, a molecular chaperone. The Tcm62p amino terminus is in the mitochondrial matrix, whereas the car boxyl terminus is accessible from the intermembrane space. Tcm62p form s a complex containing at least three SDH subunits. We propose that Tc m62p functions as a chaperone in the assembly of yeast SDH.