Peroxisomal targeting of Pichia pastoris cytochrome c

Cytochrome c (cyt c), a well studied and highly conserved mitochondrial protein involved in electron transport triggers apoptosis in a variety of eukaryotic cells when released into cytoplasm in response to apoptogenic stimuli. Surprisingly, cyt c is targeted to peroxisomes of the methylotrophic yeast, Pichia pastoris grown on methanol or oleic acid as the sole carbon source. When expressed in S. cerevisiae cells, P. pastoris cyt c (Pp-cyt c) is targeted to oleic acid-induced peroxisomes. Distinct physiological changes are observed in S. cerevisiae cells expressing Pp-cyt c such as rapid growth on fatty acid containing media, enhanced uptake of fatty acids and their assimilation into neutral lipids. We conclude that peroxisomal targeting is an inherent and unique property of Pp-cyt c and the machinery involved in the import process is conserved in other yeast species as well. We further propose a novel role for cyt c in peroxisomal fatty acid metabolism that has potential applications in engineering yeast cells for the bioconversion of fatty acids into value-added lipid products