Characterization of yeast genes homologous to human genes involved in mitochondrial and peroxisomal function

Abstract

The Saccharomyces cerevisiae genes YPR004c, YGR207c, YOR356w and YDR036c homologous to human genes involved in transfer of electrons to the respiratory chain from flavin-containing dehydrogenases (ETFA, ETFB and ETFDH) and in beta-oxidation (HADHA), were chosen for characterization. Mutations in ETFA, ETFB and ETFDH (orthologous to YPR004c, YGR207c and YOR356w, respectively) cause multiple acyl-CoA dehydrogenation deficiency, also known as glutaric aciduria II. Mutations in HADHA (orthologous to YDR036c) affect the alpha-subunit of the trifunctional enzyme that catalyzes three reactions in mitochondrial beta-oxidation of fatty acids. In previous studies, all of these yeast genes have been localized in the mitochondrion. Unlike mammalian cells, fatty acid catabolism by beta-oxidation in yeast takes place exclusively in peroxisomes. The aim of this work is to contribute to understand the functional relation between mitochondria and peroxisomes, by studying lipid catabolism in yeast cells. S. cerevisiae mutants affected in the above mentioned genes were studied for growth on several non-fermentable carbon sources and for carbon sources, which catabolism requires peroxisomal activity (oleic acid and methanol). Growth is unaffected on non-fermentable carbon sources and is decreased for all mutants only on methanol, which suggests deficiency in peroxisomal activity concomitant with normal function of mitochondria. On the other hand, ygr207c and yor356w mutant strains present growth deficiency on oleic acid, suggesting a wider peroxisomal metabolic deficiency when compared to ypr004c and ydr036c.