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© The Rockefeller University Press, 0021-9525/2000//489 $5.00
The Journal of Cell Biology, Volume 150, Number 3, , 2000 489-498

Pex11p Plays a Primary Role in Medium-Chain Fatty Acid Oxidation, a Process That Affects Peroxisome Number and Size in Saccharomyces cerevisiae

^a Department of Clinical Chemistry, Emma Children's Hospital, University of Amsterdam, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands
^b Department of Biochemistry, Emma Children's Hospital, University of Amsterdam, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands
^c Department of Pediatrics, Emma Children's Hospital, University of Amsterdam, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands
University of Amsterdam, Academic Medical Center, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.+31 20 6915519+31 20 5665159

h.f.tabak{at}amc.uva.nl

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) β-oxidation display the same phenotype as Pex11p-deficient cells. Upon closer inspection, we found that Pex11p is required for MCFA β-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 β-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.

Key Words: peroxisome • β-oxidation • peroxin • organelle multiplication • morphology

© 2000 The Rockefeller University Press

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