Pex11p plays a primary role in medium-chain fatty acid oxidation, a process that affects peroxisome number and size in Saccharomyces cerevisiae.
The Saccharomyces cerevisiae peroxisomal membrane protein Pex11p has previously been implicated in peroxisome proliferation based on morphological observations of PEX11 mutant cells. Pex11p-deficient cells fail to increase peroxisome number in response to growth on fatty acids and instead accumulate a few giant peroxisomes. We report that mutants deficient in genes required for medium-chain fatty acid (MCFA) beta-oxidation display the same phenotype as Pex11p-deficient cells. Upon closer inspection, we found that Pex11p is required for MCFA beta-oxidation. Disruption of the PEX11 gene results in impaired formation of MCFA-CoA esters as measured in intact cells, whereas their formation is normal in cell lysates. The sole S. cerevisiae MCFA-CoA synthetase (Faa2p) remains properly localized to the inner leaflet of the peroxisomal membrane in PEX11 mutant cells. Therefore, the in vivo latency of MCFA activation observed in Pex11p-deficient cells suggests that Pex11p provides Faa2p with substrate. When PEX11 mutant cells are shifted from glucose to oleate-containing medium, we observed an immediate deficiency in beta-oxidation of MCFAs whereas giant peroxisomes and a failure to increase peroxisome abundance only became apparent much later. Our observations suggest that the MCFA oxidation pathway regulates the level of a signaling molecule that modulates the number of peroxisomal structures in a cell.
Department of Clinical Chemistry, Emma Children's Hospital, University of Amsterdam, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands.
C W
CW
van Roermund
H F
HF
Tabak
M
M
van Den Berg
R J
RJ
Wanders
E H
EH
Hettema
D042962:Acyl-CoA Oxidase; D003066:Coenzyme A Ligases / Q000302:isolation & purification / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D019301:Oleic Acid / Q000378:metabolism; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000235:genetics; D000074401:Peroxins; D020675:Peroxisomes / Q000502:physiology* / Q000648:ultrastructure; D012097:Repressor Proteins; D012441:Saccharomyces cerevisiae / Q000378:metabolism* / Q000648:ultrastructure; D029701:Saccharomyces cerevisiae Proteins; D000098859:Long-Chain-Fatty-Acid-CoA Ligase
D005227:Fatty Acids; D008565:Membrane Proteins; C092128:PEX11 protein, S cerevisiae; D000074401:Peroxins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D019301:Oleic Acid; D010088:Oxidoreductases; D042962:Acyl-CoA Oxidase; C467991:POX1 protein, S cerevisiae; D003066:Coenzyme A Ligases; C019805:butyryl-CoA synthetase; C090799:FAA2 protein, S cerevisiae; D000098859:Long-Chain-Fatty-Acid-CoA Ligase