Human mitochondrial pyruvate carrier 2 as an autonomous membrane transporter

Scientific Reports
Raghavendra Sashi Krishna NagampalliAndre Luis Berteli Ambrosio

Abstract

The active transport of glycolytic pyruvate across the inner mitochondrial membrane is thought to involve two mitochondrial pyruvate carrier subunits, MPC1 and MPC2, assembled as a 150 kDa heterotypic oligomer. Here, the recombinant production of human MPC through a co-expression strategy is first described; however, substantial complex formation was not observed, and predominantly individual subunits were purified. In contrast to MPC1, which co-purifies with a host chaperone, we demonstrated that MPC2 homo-oligomers promote efficient pyruvate transport into proteoliposomes. The derived functional requirements and kinetic features of MPC2 resemble those previously demonstrated for MPC in the literature. Distinctly, chemical inhibition of transport is observed only for a thiazolidinedione derivative. The autonomous transport role for MPC2 is validated in cells when the ectopic expression of human MPC2 in yeast lacking endogenous MPC stimulated growth and increased oxygen consumption. Multiple oligomeric species of MPC2 across mitochondrial isolates, purified protein and artificial lipid bilayers suggest functional high-order complexes. Significant changes in the secondary structure content of MPC2, as probed by synchrotron radia...Continue Reading

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Citations

Dec 6, 2019·Hepatology International·Katharina C ReimerFrank Tacke
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Jan 22, 2021·Cell Death and Differentiation·Mariana Fernandez-Caggiano, Philip Eaton
Oct 20, 2021·Journal of Chemical Information and Modeling·Liang XuLiao Y Chen

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Methods Mentioned

BETA
enzymatic assay
gel-filtration
confocal microscopy
Circular Dichroism
co-immunoprecipitation
PCR
size-exclusion
gel filtration
dynamic light scattering
RNA-Seq

Software Mentioned

Mascot engine
Mascot Distiller
Metacore
Clarivate Analytics
MassLynx
R
Enspire

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