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Pedersen, M. P.

Publications and source records attributed to Pedersen, M. P..

2 recordsLinked to original sources

Integrative Omics reveals changes in the cellular landscape of yeast without peroxisomes

Peroxisomes are organelles that are crucial for cellular metabolism. However, these organelles play also important roles in non-metabolic processes, such as signalling. To uncover the consequences of peroxisome deficiency, we compared two extremes, namely Saccharomyces cerevisiae wild-type and pex3 cells, which lack functional peroxisomes, employing transcriptomics and quantitative proteomics technology. Cells were grown on acetate, a carbon source that involves peroxisomal enzymes of the glyoxylate cycle and does not repress peroxisomal proteins. Transcripts of peroxisomal {beta}-oxidation genes and the corresponding proteins were enhanced in pex3 cells. Peroxisome-deficiency also caused reduced levels of membrane bound peroxins, while the soluble receptors Pex5 and Pex7 were enhanced at the protein level. In addition, we observed alterations in non-peroxisomal transcripts and proteins, especially mitochondrial proteins involved in respiration or import processes. Our results not only reveal the impact of the absence of peroxisomes in yeast, but also represent a rich resource of candidate genes/proteins that are relevant in peroxisome biology. SummaryOmics comparison of wild-type and peroxisome-deficient (pex3) yeast cells uncovered processes that are affected by loss of peroxisomes. {beta}-oxidation enzymes were upregulated, whereas most peroxins were decreased. Also, several non-peroxisomal transcripts/proteins were significantly altered. Our data represent a rich source of candidate genes connected to peroxisome biology.

cell biology↗

The Hansenula polymorpha Mitochondrial Carrier Family proteins Mir1 and Aac2 are dually localized at peroxisomes and mitochondria

Peroxisomes are ubiquitous cell organelles involved in various metabolic pathways. In order to properly function, several cofactors, substrates and products of peroxisomal enzymes need to pass the organellar membrane. So far only a few transporter proteins have been identified. We analysed peroxisomal membrane fractions purified from the yeast Hansenula polymorpha by untargeted label-free quantitation mass spectrometry. As expected, several known peroxisome-associated proteins were enriched in the peroxisomal membrane fraction. In addition, several other proteins were enriched, including mitochondrial transport proteins. Localization studies revealed that two of them, the mitochondrial carrier family proteins Aac2 and Mir1, have a dual localization on mitochondria and peroxisomes. To better understand the molecular mechanisms of dual sorting, we tested the localization of Mir1 in cells lacking Pex3 or Pex19, two peroxins that play a role in targeting of peroxisomal membrane proteins. In these cells Mir1 only localized to mitochondria, indicating that Pex3 and Pex19 are required to sort Mir1 to peroxisomes. Analysis of the localization of various truncated versions of Mir1 in wild-type H. polymorpha cells revealed that several localized to mitochondria, but only one, consisting of the transmembrane domains 3-6, was peroxisomal. Peroxisomal localization of this construct was lost in a MIR1 deletion strain, indicating that full length Mir1 was required for the localization of the truncated protein to peroxisomes. Our data suggest that only full length Mir1 sorts to peroxisomes, while Mir1 contains multiple regions with mitochondrial sorting information.

cell biology↗