A plant-like mitochondrial carrier family protein facilitates mitochondrial transport of di- and tricarboxylates in Trypanosoma brucei

Colasante, Claudia; Zheng, Fuli; Kemp, Cordula; Voncken, Frank

Abstract

The procyclic form of the human parasite Trypanosoma brucei harbors one single, large mitochondrion containing all tricarboxylic acid (TCA) cycle enzymes and respiratory chain complexes present also in higher eukaryotes. Metabolite exchange among subcellular compartments such as the cytoplasm, the mitochondrion, and the peroxisomes is crucial for redox homeostasis and for metabolic pathways whose enzymes are dispersed among different organelles. In higher eukaryotes, mitochondrial carrier family (MCF) proteins transport TCA-cycle intermediates across the inner mitochondrial membrane. Previously, we identified several MCF members that are essential for T. brucei survival. Among these, only one MCF protein, TbMCP12, potentially could transport dicarboxylates and tricarboxylates. Here, we conducted phylogenetic and sequence analyses and functionally characterised TbMCP12 in vivo. Our results suggested that similarly to its homologues in plants, TbMCP12 transports both dicarboxylates and tricarboxylates across the mitochondrial inner membrane. Deleting this carrier in T. brucei was not lethal, while its overexpression was deleterious. Our results suggest that the intracellular abundance of TbMCP12 is an important regulatory element for the NADPH balance and mitochondrial ATP-production.

Citation

Colasante, C., Zheng, F., Kemp, C., & Voncken, F. (2018). A plant-like mitochondrial carrier family protein facilitates mitochondrial transport of di- and tricarboxylates in Trypanosoma brucei. Molecular and Biochemical Parasitology, 221, 36-51. https://doi.org/10.1016/j.molbiopara.2018.03.003

• Journal Article Type: Article
• Acceptance Date: Mar 21, 2018
• Online Publication Date: Mar 23, 2018
• Publication Date: 2018-04
• Deposit Date: Aug 14, 2019
• Journal: Molecular and Biochemical Parasitology
• Print ISSN: 0166-6851
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 221
• Pages: 36-51
• DOI: https://doi.org/10.1016/j.molbiopara.2018.03.003
• Keywords: Mitochondrial transport, Trypanosoma brucei, Energy metabolism, MCF-proteins, Dicarboxylate, Tricarboxylate
• Public URL: https://hull-repository.worktribe.com/output/2360330
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S0166685117301639
• Additional Information: This article is maintained by: Elsevier; Article Title: A plant-like mitochondrial carrier family protein facilitates mitochondrial transport of di- and tricarboxylates in Trypanosoma brucei; Journal Title: Molecular and Biochemical Parasitology; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.molbiopara.2018.03.003; Content Type: article; Copyright: © 2018 Elsevier B.V. All rights reserved.