Multiple, redundant carboxylic acid transporters support mitochondrial metabolism in Plasmodium falciparum.

ABSTRACT: The mitochondrion of the deadliest human malaria parasite, Plasmodium falciparum, is an essential source of cellular acetyl-CoA during the asexual blood-stage of the parasite life cycle. Blocking mitochondrial acetyl-CoA synthesis leads to a hypoacetylated proteome and parasite death. We previously determined that mitochondrial acetyl-CoA is primarily synthesized from glucose-derived pyruvate by α-ketoacid dehydrogenases. Here, we asked if inhibiting the import of glycolytic pyruvate across the mitochondrial inner membrane would affect acetyl-CoA production and, thus, could be a potential target for antimalarial drug development. We selected the two predicted mitochondrial pyruvate carrier proteins, PfMPC1 (PF3D7_1340800) and PfMPC2 (PF3D7_1470400), for genetic KO and isotopic metabolite t

SUBMITTER: Rajaram K 

PROVIDER: S-EPMC12268629 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature