Distribution and Functional Analysis of Isocitrate Dehydrogenases across Kinetoplastids.

Autor:	Chmelová Ľ; Life Science Research Centre, Faculty of Science, University of Ostrava, Ostrava, Czechia., Záhonová K; Life Science Research Centre, Faculty of Science, University of Ostrava, Ostrava, Czechia.; Institute of Parasitology, Biology Centre, Czech Academy of Sciences, České Budějovice, Czechia.; Department of Parasitology, Faculty of Science, Charles University, BIOCEV, Vestec, Czechia.; Division of Infectious Diseases, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada., Albanaz ATS; Life Science Research Centre, Faculty of Science, University of Ostrava, Ostrava, Czechia., Hrebenyk L; Life Science Research Centre, Faculty of Science, University of Ostrava, Ostrava, Czechia., Horváth A; Department of Biochemistry, Faculty of Natural Sciences, Comenius University, Bratislava, Slovakia., Yurchenko V; Life Science Research Centre, Faculty of Science, University of Ostrava, Ostrava, Czechia., Škodová-Sveráková I; Life Science Research Centre, Faculty of Science, University of Ostrava, Ostrava, Czechia.; Institute of Parasitology, Biology Centre, Czech Academy of Sciences, České Budějovice, Czechia.; Department of Biochemistry, Faculty of Natural Sciences, Comenius University, Bratislava, Slovakia.
Jazyk:	angličtina
Zdroj:	Genome biology and evolution [Genome Biol Evol] 2024 Mar 02; Vol. 16 (3).
DOI:	10.1093/gbe/evae042
Abstrakt:	Isocitrate dehydrogenase is an enzyme converting isocitrate to α-ketoglutarate in the canonical tricarboxylic acid (TCA) cycle. There are three different types of isocitrate dehydrogenase documented in eukaryotes. Our study points out the complex evolutionary history of isocitrate dehydrogenases across kinetoplastids, where the common ancestor of Trypanosomatidae and Bodonidae was equipped with two isoforms of the isocitrate dehydrogenase enzyme: the NADP+-dependent isocitrate dehydrogenase 1 with possibly dual localization in the cytosol and mitochondrion and NADP+-dependent mitochondrial isocitrate dehydrogenase 2. In the extant trypanosomatids, isocitrate dehydrogenase 1 is present only in a few species suggesting that it was lost upon separation of Trypanosoma spp. and replaced by the mainly NADP+-dependent cytosolic isocitrate dehydrogenase 3 of bacterial origin in all the derived lineages. In this study, we experimentally demonstrate that the omnipresent isocitrate dehydrogenase 2 has a dual localization in both mitochondrion and cytosol in at least four species that possess only this isoform. The apparent lack of the NAD+-dependent isocitrate dehydrogenase activity in trypanosomatid mitochondrion provides further support to the existence of the noncanonical TCA cycle across trypanosomatids and the bidirectional activity of isocitrate dehydrogenase 3 when operating with NADP+ cofactor instead of NAD+. This observation can be extended to all 17 species analyzed in this study, except for Leishmania mexicana, which showed only low isocitrate dehydrogenase activity in the cytosol. The variability in isocitrate oxidation capacity among species may reflect the distinct metabolic strategies and needs for reduced cofactors in particular environments. (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)
Databáze:	MEDLINE
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