Calcium-sensitive pyruvate dehydrogenase phosphatase is required for energy metabolism, growth, differentiation, and infectivity of Trypanosoma cruzi.

ABSTRACT: In vertebrate cells, mitochondrial Ca²⁺ uptake by the mitochondrial calcium uniporter (MCU) leads to Ca²⁺-mediated stimulation of an intramitochondrial pyruvate dehydrogenase phosphatase (PDP). This enzyme dephosphorylates serine residues in the E1α subunit of pyruvate dehydrogenase (PDH), thereby activating PDH and resulting in increased ATP production. Although a phosphorylation/dephosphorylation cycle for the E1α subunit of PDH from nonvertebrate organisms has been described, the Ca²⁺-mediated PDP activation has not been studied. In this work, we investigated the Ca²⁺ sensitivity of two recombinant PDPs from the protozoan human parasites Trypanosoma cruzi (TcPDP) and T. brucei (TbPDP) and generated a TcPDP-KO cell line to

SUBMITTER: Lander N 

PROVIDER: S-EPMC6231137 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature