MUTATIONS IN THE PAY5 GENE OF THE YEAST YARROWIA-LIPOLYTICA CAUSE THEACCUMULATION OF MULTIPLE SUBPOPULATIONS OF PEROXISOMES

We previously reported the cloning of the PAYS gene of the yeast Yarro wia lipolytica by complementation of the peroxisome assembly mutant pa y5-1 (Eitzen, G. A., Titorenko, V. I., Smith, J. J., Veenhuis, M., Szi lard, R. K., and Rachubinski, R. A. (1996) J Biol. Chem. 271, 20300-20 306). The peroxisomal integral membrane protein Pay5p is a homologue o f mammalian PAF-1 proteins, which are essential for peroxisome assembl y and whose mutation in humans results in peroxisome biogenesis disord ers, Mutations in the PAYS gene result in the accumulation of three di stinct peroxisomal subpopulations. These subpopulations are characteri zed by differences in 1) buoyant density, 2) the relative distribution of peroxisomal matrix and membrane proteins, 3) the efficiency of imp ort of several peroxisomal matrix proteins, and 4) the phospholipid le vels of peroxisomal membranes. These data, together with the analysis of temporal changes in the relative abundance of individual peroxisoma l subpopulations in pay5 mutants, suggest that these subpopulations re present intermediates in a multistep peroxisome assembly pathway norma lly operating in yeast cells.