Abstract
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.
Highlights
Eukaryotic cells are thought to have evolved ϳ1.5 billion years ago
In cells deleted for the function of Mpp1p the levels of various proteins involved in peroxisome biogenesis and function are reduced compared with wild type or, in the case of the matrix protein dihydroxyacetone synthase, fully absent
We report the identification of a novel H. polymorpha transcription factor, Mpp1p, which is involved in the regulation of peroxisomal proteins
Summary
Eukaryotic cells are thought to have evolved ϳ1.5 billion years ago. The development of cell organelles allowed primitive eukaryotes to compartmentalize specific cellular functions. In the methylotrophic yeast Hansenula polymorpha peroxisomes are essential to support growth of cells on media containing methanol as the sole source of carbon and energy. Under these conditions many organelles that contain the key enzymes involved in methanol metabolism, alcohol oxidase (AO), dihydroxyacetone synthase (DHAS), and catalase, develop in the cells. Morphological data suggest that in each cell generally a single (or few) small peroxisome(s) escape(s) the degradation process The resistance of these organelles to degradation is thought to be of physiological advantage in that it allows the cells to quickly adapt to new environments that require new peroxisome functions. These single organelles are protected from selective degradation upon exposure of cells to excess glucose
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