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A Mitochondrial Pyruvate Carrier Required for Pyruvate Uptake in Yeast, Drosophila, and Humans.

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Title: A Mitochondrial Pyruvate Carrier Required for Pyruvate Uptake in Yeast, Drosophila, and Humans.
Authors: Bricker, Daniel K., Taylor, Eric B., Schell, John C., Orsak, Thomas, Boutron, Audrey, Yu-Chan Chen, Cox, James E., Cardon, Caleb M., Van Vranken, Jonathan G., Dephoure, Noah, Redin, Claire, Boudina, Sihem, Gygi, Steven P., Brivet, Michèle, Thummel, Carl S., Rutter, Jared
Source: Science (pre-March 2025). 7/6/2012, Vol. 337 Issue 6090, p96-100. 5p.
Subjects: Pyruvates, Mitochondrial proteins, Biological transport, Carrier proteins, Mitochondrial membranes, Carbon metabolism, Fungal proteins, Human proteins, Drosophila proteins
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-kitodalton 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. [ABSTRACT FROM AUTHOR]
Copyright of Science (pre-March 2025) is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Data: A Mitochondrial Pyruvate Carrier Required for Pyruvate Uptake in Yeast, Drosophila, and Humans.
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  Data: <searchLink fieldCode="AR" term="%22Bricker%2C+Daniel+K%2E%22">Bricker, Daniel K.</searchLink><br /><searchLink fieldCode="AR" term="%22Taylor%2C+Eric+B%2E%22">Taylor, Eric B.</searchLink><br /><searchLink fieldCode="AR" term="%22Schell%2C+John+C%2E%22">Schell, John C.</searchLink><br /><searchLink fieldCode="AR" term="%22Orsak%2C+Thomas%22">Orsak, Thomas</searchLink><br /><searchLink fieldCode="AR" term="%22Boutron%2C+Audrey%22">Boutron, Audrey</searchLink><br /><searchLink fieldCode="AR" term="%22Yu-Chan+Chen%22">Yu-Chan Chen</searchLink><br /><searchLink fieldCode="AR" term="%22Cox%2C+James+E%2E%22">Cox, James E.</searchLink><br /><searchLink fieldCode="AR" term="%22Cardon%2C+Caleb+M%2E%22">Cardon, Caleb M.</searchLink><br /><searchLink fieldCode="AR" term="%22Van+Vranken%2C+Jonathan+G%2E%22">Van Vranken, Jonathan G.</searchLink><br /><searchLink fieldCode="AR" term="%22Dephoure%2C+Noah%22">Dephoure, Noah</searchLink><br /><searchLink fieldCode="AR" term="%22Redin%2C+Claire%22">Redin, Claire</searchLink><br /><searchLink fieldCode="AR" term="%22Boudina%2C+Sihem%22">Boudina, Sihem</searchLink><br /><searchLink fieldCode="AR" term="%22Gygi%2C+Steven+P%2E%22">Gygi, Steven P.</searchLink><br /><searchLink fieldCode="AR" term="%22Brivet%2C+Michèle%22">Brivet, Michèle</searchLink><br /><searchLink fieldCode="AR" term="%22Thummel%2C+Carl+S%2E%22">Thummel, Carl S.</searchLink><br /><searchLink fieldCode="AR" term="%22Rutter%2C+Jared%22">Rutter, Jared</searchLink>
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  Data: <searchLink fieldCode="JN" term="%22Science+%28pre-March+2025%29%22">Science (pre-March 2025)</searchLink>. 7/6/2012, Vol. 337 Issue 6090, p96-100. 5p.
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  Data: <searchLink fieldCode="DE" term="%22Pyruvates%22">Pyruvates</searchLink><br /><searchLink fieldCode="DE" term="%22Mitochondrial+proteins%22">Mitochondrial proteins</searchLink><br /><searchLink fieldCode="DE" term="%22Biological+transport%22">Biological transport</searchLink><br /><searchLink fieldCode="DE" term="%22Carrier+proteins%22">Carrier proteins</searchLink><br /><searchLink fieldCode="DE" term="%22Mitochondrial+membranes%22">Mitochondrial membranes</searchLink><br /><searchLink fieldCode="DE" term="%22Carbon+metabolism%22">Carbon metabolism</searchLink><br /><searchLink fieldCode="DE" term="%22Fungal+proteins%22">Fungal proteins</searchLink><br /><searchLink fieldCode="DE" term="%22Human+proteins%22">Human proteins</searchLink><br /><searchLink fieldCode="DE" term="%22Drosophila+proteins%22">Drosophila proteins</searchLink>
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  Data: 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-kitodalton 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. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Science (pre-March 2025) is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=pbh&AN=77929635
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        Value: 10.1126/science.1218099
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        Text: English
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      – SubjectFull: Biological transport
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      – SubjectFull: Drosophila proteins
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