Peroxisomes (red) and mitochondria (green) in Ustilago maydis.
Credit: Martin Schuster.

New model gives scientists insight into cells’ fat-metabolisers

Recent research from the University of Exeter has demonstrated that Ustilago maydis, a fungal pathogen, can act as an excellent model to study the interplay of the fat-metabolising organelles of mammalian cells.

The organelles in question are mitochondria – generators of chemical energy – and peroxisomes. Peroxisomes have a variety of functions, which include making and metabolising cellular fats; these fats are an essential component of the cell membrane surrounding every cell, and protect the nerves.

Resultantly, peroxisomal dysfunctions are linked to severe medical conditions affecting the nervous system and in metabolic diseases, such as X-linked adrenoleukodystrophy, a progressive disorder affecting the central nervous system of 1 in every 17,000 newborns.

In a study published in Biochimica et Biophysica Acta, the authors - including Professor Gero Steinberg and Dr. Michael Schrader - found that U. maydis uses both peroxisomal and mitochondrial enzymes together to break down fats; this was previously only seen in animal cells (including human cells), and shown not to be the case in baker’s yeast or plants, which only use peroxisomes for fatty acid breakdown by β-oxidation. 

This collaborative approach combined study of mammalian cells, and use of fungi with mutations to prevent peroxisomes forming, in order to reveal which fatty acid chains were broken down by the mitochondria, and which by peroxisomes. In establishing that U. maydis uses a complex and complete inventory of enzymes resembling that of animals, the authors validated this as a suitable model for studying the interplay between mitochondria and peroxisomes.

“As they both regulate cellular lipid metabolism, ROS (reactive oxygen species) homeostasis and even anti-viral defence, their cooperative role in cellular signalling has important implications for viral combat, cellular ageing, and age-related disorders such as neurodegeneration and diabetes,” commented Dr. Schrader on the importance of this research.

Mitochondria and peroxisomes use separate, specific enzymes to break down fatty acid chains of particular lengths, but this paper also showed that typically “mitochondrial” enzymes actually also function at peroxisomes in fungi, and in mammals. The authors suggest that these enzymes may work together to regulate release of hydrogen peroxide into the cells, which has important signalling functions.

Being able to utilise fungal systems, such as U. maydis, is useful in understanding the fundamentals of cell biology; they rapidly multiply, we can easily alter their genetics, and they use many of the same proteins and processes as mammalian cells, as supported by this work.

Date: 29 October 2014

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