Ubiquinone and bc1 assembly: Is substrate synthesis required for respiratory enzyme assembly?

HAYAA F. HASHEMI; JULIA A. CRICCO; PAUL A. COBINE

Montgomery, AL

Conferencia; 96th Annual Southeastern Branch ASM Conference; 2010

American Society of Microbiology

Ubiquinone and bc1 assembly: Is substrate synthesis required for respiratory enzyme assembly? Hayaa F. Hashemi1, Julia A. Cricco2, and Paul A. Cobine1 1. Department of Biological Sciences, Auburn University, Auburn, AL 2. Instituto de Biologia Molecular y Celular de Rosario, CONICET‐UNR, Rosario, Argentina The bc1 complex, or ubiquinol-cytochrome c oxidoreductase, is part of the mitochondrial electron transport chain, which is responsible for respiration and ATP generation in eukaryotes. Mutations in the indvidual subunits, and one assembly factor, have been implicated in disorders such as Leber's myopathy, GRACILE syndrome and infantile cardiomyopathy. Although six assembly factors have been identified, the exact sequential order of bc1 assembly and the mechanism of these assembly factors is not well understood. A detailed understanding of the bc1 assembly mechanism, is important to understanding the pathology of bc1 complex disorders. The bc1 complex is made up of 10 subunits, 9 of which are encoded by nuclear genes while one is mitochondrially encoded. Two bc1 subunits (Cob and Cyt1) have heme prosthetic groups required for electron transfer from ubiquinol to cytochrome c. Total heme concentrations in mitochondria appear to directly correlate with the stability of bc1. In the present study, we have used Saccharomyces cerevisiae to study bc1 assembly pathway. Our data suggests that in coq mutants that are unable to synthesize ubiquinone, bc1 assembly is stalled. These mutants have dramatically lower heme b levels compared to wild-type. Exogenous supplementation with ubiquinone does not increase heme b concentrations in coq mutants. These results imply that the ubiquinone synthesis complex is required for formation/stability of the bc1 complex.