• Home
  • Search Results
  • Thiazolidinediones are acute, specific inhibitors of the mitochondrial pyruvate carrier.

Thiazolidinediones are acute, specific inhibitors of the mitochondrial pyruvate carrier.

Proceedings of the National Academy of Sciences of the United States of America (2013-03-21)
Ajit S Divakaruni, Sandra E Wiley, George W Rogers, Alexander Y Andreyev, Susanna Petrosyan, Mattias Loviscach, Estelle A Wall, Nagendra Yadava, Alejandro P Heuck, David A Ferrick, Robert R Henry, William G McDonald, Jerry R Colca, Melvin I Simon, Theodore P Ciaraldi, Anne N Murphy
ABSTRACT

Facilitated pyruvate transport across the mitochondrial inner membrane is a critical step in carbohydrate, amino acid, and lipid metabolism. We report that clinically relevant concentrations of thiazolidinediones (TZDs), a widely used class of insulin sensitizers, acutely and specifically inhibit mitochondrial pyruvate carrier (MPC) activity in a variety of cell types. Respiratory inhibition was overcome with methyl pyruvate, localizing the effect to facilitated pyruvate transport, and knockdown of either paralog, MPC1 or MPC2, decreased the EC50 for respiratory inhibition by TZDs. Acute MPC inhibition significantly enhanced glucose uptake in human skeletal muscle myocytes after 2 h. These data (i) report that clinically used TZDs inhibit the MPC, (ii) validate that MPC1 and MPC2 are obligatory components of facilitated pyruvate transport in mammalian cells, (iii) indicate that the acute effect of TZDs may be related to insulin sensitization, and (iv) establish mitochondrial pyruvate uptake as a potential therapeutic target for diseases rooted in metabolic dysfunction.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
UK-5099, ≥98% (HPLC)

Social Media

LinkedIn icon
Twitter icon
Facebook Icon
Instagram Icon

MilliporeSigma

Research. Development. Production.

We are a leading supplier to the global Life Science industry with solutions and services for research, biotechnology development and production, and pharmaceutical drug therapy development and production.

© 2021 Merck KGaA, Darmstadt, Germany and/or its affiliates. All Rights Reserved.

Reproduction of any materials from the site is strictly forbidden without permission.