Journal article
A Mitochondrial Pyruvate Carrier Required for Pyruvate Uptake in Yeast, Drosophila, and Humans
Science (American Association for the Advancement of Science), Vol.337(6090), pp.96-100
07/06/2012
DOI: 10.1126/science.1218099
PMCID: PMC3690818
PMID: 22628558
Abstract
Pyruvate constitutes a critical branch point in cellular carbon metabolism. We have identified two proteins, Mpc1 and Mpc2, as essential for mitochondrial pyruvate transport in yeast,
Drosophila
, and humans. Mpc1 and Mpc2 associate to form an ~150-kilodalton complex in the inner mitochondrial membrane. Yeast and
Drosophila
mutants lacking
MPC1
display impaired pyruvate metabolism, with an accumulation of upstream metabolites and a depletion of tricarboxylic acid cycle intermediates. Loss of yeast Mpc1 results in defective mitochondrial pyruvate uptake, and silencing of
MPC1
or
MPC2
in mammalian cells impairs pyruvate oxidation. A point mutation in
MPC1
provides resistance to a known inhibitor of the mitochondrial pyruvate carrier. Human genetic studies of three families with children suffering from lactic acidosis and hyperpyruvatemia revealed a causal locus that mapped to
MPC1
, changing single amino acids that are conserved throughout eukaryotes. These data demonstrate that Mpc1 and Mpc2 form an essential part of the mitochondrial pyruvate carrier.
Details
- Title: Subtitle
- A Mitochondrial Pyruvate Carrier Required for Pyruvate Uptake in Yeast, Drosophila, and Humans
- Creators
- Daniel K Bricker - Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT 84112, USAEric B Taylor - Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112, USAJohn C Schell - Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112, USAThomas Orsak - Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112, USAAudrey Boutron - Laboratoire de Biochimie, AP-HP Hôpital de Bicêtre, Le Kremlin Bicêtre, FranceYu-Chan Chen - Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112, USAJames E Cox - Metabolomics Core Research Facility, University of Utah School of Medicine, Salt Lake City, UT 84112, USACaleb M Cardon - Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112, USAJonathan G Van Vranken - Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112, USANoah Dephoure - Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USAClaire Redin - Institut de Genetique et de Biologie Moleculaire et Cellulaire (IGBMC), Strasbourg, FranceSihem Boudina - Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT 84112, USASteven P Gygi - Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USAMichèle Brivet - Laboratoire de Biochimie, AP-HP Hôpital de Bicêtre, Le Kremlin Bicêtre, FranceCarl S Thummel - Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT 84112, USAJared Rutter - Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
- Resource Type
- Journal article
- Publication Details
- Science (American Association for the Advancement of Science), Vol.337(6090), pp.96-100
- DOI
- 10.1126/science.1218099
- PMID
- 22628558
- PMCID
- PMC3690818
- ISSN
- 0036-8075
- eISSN
- 1095-9203
- Grant note
- R24 DK092784 || DK / National Institute of Diabetes and Digestive and Kidney Diseases : NIDDK P30 HL101310 || HL / National Heart, Lung, and Blood Institute : NHLBI
- Language
- English
- Date published
- 07/06/2012
- Academic Unit
- Molecular Physiology and Biophysics
- Record Identifier
- 9984025668902771
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