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J. Biol. Chem., Vol. 278, Issue 42, 40749-40756, October 17, 2003

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Transcriptional Down-regulation of Peroxisome Numbers Affects Selective Peroxisome Degradation in Hansenula polymorpha^*

Adriana Nívea Leão-Helder, Arjen M. Krikken, Ida J. van der Klei, Jan A. K. W. Kiel and Marten Veenhuis 

From the Eukaryotic Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Haren 9750 AA, The Netherlands

We have isolated and characterized a novel transcription factor of Hansenula polymorpha that is involved in the regulation of peroxisomal protein levels. This protein, designated Mpp1p, belongs to the family of Zn(II)₂Cys₆ proteins. In cells deleted for the function of Mpp1p the levels of various proteins involved in peroxisome biogenesis (peroxins) and function (enzymes) are reduced compared with wild type or, in the case of the matrix protein dihydroxyacetone synthase, fully absent. Also, upon induction of mpp1 cells on methanol, the number of peroxisomes was strongly reduced relative to wild type cells and generally amounted to one organelle per cell. Remarkably, this single organelle was not susceptible to selective peroxisome degradation (pexophagy) and remained unaffected during exposure of methanol-induced cells to excess glucose conditions. We show that this mechanism is a general phenomenon in H. polymorpha in the case of cells that contain only a single peroxisome.

Received for publication, April 17, 2003 , and in revised form, July 22, 2003.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank^TM/EBI Data Bank with accession number(s) AY190521.

^* This work was supported in part by a grant from Coordenação de Aperfeiçoamento de Pessoal de Niável Superior-Brasilia/Universidade do Estado do Rio de Janeiro, Brazil (to A. N. L.-H.) and by a grant from Aard-en Levens Wetenschappen, which is subsidized by the Dutch Organization for the Advancement of Pure Research (to I. J. v. d. K. and J. A. K. W. K.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Eukaryotic Microbiology, GBB, University of Groningen, P. O. Box 14, Haren 9750 AA, The Netherlands. Tel.: 31-50-3632176; Fax: 31-50-3638280; E-mail: M.Veenhuis{at}biol.rug.nl.

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