Mitochondrial targeting of glycolysis in a major lineage of eukaryotes.
Preprint posted on 31 January 2018 https://www.biorxiv.org/content/early/2018/01/31/257790
Article now published in Genome Biology and Evolution at http://dx.doi.org/10.1093/gbe/evy164
Here the authors show a novel location for a central metabolic pathway: the enzymes of the latter half of glycolysis, normally localised in the cytoplasm, are targeted to the mitochondria in certain Stramenopiles (Heterokonts).
Selected by Ellis O'NeillCategories: biochemistry, cell biology, microbiology
Overview
I chose this pre-print because it is always nice to find exceptions to the rule in biology. We think we have a pretty good idea about core metabolic pathways, but there are still some unusual twists, as shown in this work. In most Eukaryotes, the ten enzymes of glycolysis are located in the cytosol, and the product, pyruvate, is imported into the mitochondria for further respiration in the Krebs cycle. In this work, the authors identified mitochondrial targeting sequences in the genes for the latter six enzymes of glycolysis in the human pathogen Blastocystis, a Stramenopile (Heterokont). In order to show these sequences are functional, they used them to target GFP to the mitochondria of Phaeodactylum, an alga in the same supergroup. These cells showed enzyme activity in cellular fractions corresponding to mitochondria and the activity was protected from proteases. They then identified mitochondrial targeting sequences on these enzymes in a range of related organisms, suggesting this is a widespread phenomenon in this group. Interestingly, Kinetoplastids, such as Trypanosomes, also have glycolysis compartmentation, with nine enzymes in the glycosome. Whilst this is another example of a pathogen with an unusual location of central metabolic enzymes, this doesn’t necessarily indicate a trend, as it is more likely due to the fact that human pathogens are more intensely studied.
Future Outlook
This work advances the idea that glycolysis was originally located in the mitochondrion of the ancestral bacterium. This remains to be shown; a much wider survey of these genes – to see if the trait is polyphyletic – would help to bolster this argument. The sparse sequencing in many branches of the tree of life complicates this analysis.
The authors also point out that a new transporter is needed to import the triose phosphate metabolic intermediates into the mitochondrion, and this may represent a viable drug target against human or plant pathogens that show this ‘split’ glycolysis.
Further Reading
A review of the compartmentation of glycolysis in the Kinetoplastid glycosome. (https://www.sciencedirect.com/science/article/pii/S0167488915003080)
New work in Science highlights alternatives to central metabolic pathways. (http://science.sciencemag.org/content/359/6375/517.full, http://science.sciencemag.org/content/359/6375/559, http://science.sciencemag.org/content/359/6375/563)
Posted on: 13 February 2018 , updated on: 28 March 2018
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