publication . Other literature type . Article . 2018

Human mitochondrial pyruvate carrier 2 as an autonomous membrane transporter

Raghavendra Sashi Krishna Nagampalli; José Edwin Neciosup Quesñay; Douglas Adamoski; Zeyaul Islam; James Birch; Heitor Gobbi Sebinelli; Richard Marcel Bruno Moreira Girard; Carolline Fernanda Rodrigues Ascenção; Angela Maria Fala; Bianca Alves Pauletti; ...
  • Published: 22 Feb 2018
  • Publisher: Springer Science and Business Media LLC
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 previous...
Subjects
free text keywords: PROTEÍNAS DA MEMBRANA, PROTEÍNAS DE TRANSPORTE, PARASITOLOGIA, ORGANELAS CELULARES, MITOCÔNDRIAS, AMINOÁCIDOS, TRANSPORTE BIOLÓGICO, TRANSPORTE ATRAVÉS DA MEMBRANA, Article, Multidisciplinary, Glycolysis, Protein secondary structure, Mitochondrial pyruvate carrier 2, Lipid bilayer, Inner mitochondrial membrane, Transporter, Biophysics, Chaperone (protein), biology.protein, biology, Chemistry, Pyruvate transport
Funded by
WT| A laboratory for membrane protein structural biology
Project
  • Funder: Wellcome Trust (WT)
  • Project Code: 202892
  • Funding stream: Molecular Basis of Cell Function
,
WT| The Membrane Protein Laboratory at Diamond Light Source.
Project
  • Funder: Wellcome Trust (WT)
  • Project Code: 099165
  • Funding stream: Cellular and Molecular Neuroscience
46 references, page 1 of 4

Halestrap, AP, Denton, RM. Specific inhibition of pyruvate transport in rat liver mitochondria and human erythrocytes by alpha-cyano-4-hydroxycinnamate. Biochem. J.. 1974; 138: 313-316 [OpenAIRE] [PubMed] [DOI]

Bricker, DK. A mitochondrial pyruvate carrier required for pyruvate uptake in yeast, Drosophila, and humans. Science. 2012; 337: 96-100 [OpenAIRE] [PubMed] [DOI]

Herzig, S. Identification and Functional Expression of the Mitochondrial Pyruvate Carrier. Science (80-.).. 2012; 337: 93-96 [OpenAIRE] [DOI]

Schell, JCC. A Role for the Mitochondrial Pyruvate Carrier as a Repressor of the Warburg Effect and Colon Cancer Cell Growth. Mol. Cell. 2014; 56: 400-413 [OpenAIRE] [PubMed] [DOI]

Vacanti, NMM. Regulation of Substrate Utilization by the Mitochondrial Pyruvate Carrier. Mol. Cell. 2014; 56: 425-435 [OpenAIRE] [PubMed] [DOI]

Bender, T, Pena, G, Martinou, JJ-C. Regulation of mitochondrial pyruvate uptake by alternative pyruvate carrier complexes. EMBO J.. 2015; 34: 1-14 [OpenAIRE] [PubMed] [DOI]

Vigueira, PA. Mitochondrial Pyruvate Carrier 2 Hypomorphism in Mice Leads to Defects in Glucose-Stimulated Insulin Secretion. Cell Rep.. 2014; 7: 2042-2053 [OpenAIRE] [PubMed] [DOI]

8.Vanderperre, B. et al. Embryonic Lethality of Mitochondrial Pyruvate Carrier 1 Deficient Mouse Can Be Rescued by a Ketogenic Diet. PLoS Genet. 12, (2016).

Vanderperre, B, Bender, T, Kunji, ERS, Martinou, JC. Mitochondrial pyruvate import and its effects on homeostasis. Curr. Opin. Cell Biol.. 2015; 33: 35-41 [OpenAIRE] [PubMed] [DOI]

Compan, V. Monitoring Mitochondrial Pyruvate Carrier Activity in Real Time Using a BRET-Based Biosensor: Investigation of the Warburg Effect. Mol. Cell. 2015; 59: 491-501 [OpenAIRE] [PubMed] [DOI]

Liang, L, Li, Q, Huang, L, Li, D, Li, X. Sirt3 binds to and deacetylates mitochondrial pyruvate carrier 1 to enhance its activity. Biochem. Biophys. Res. Commun.. 2015; 468: 807-812 [OpenAIRE] [PubMed] [DOI]

Halestrap, AP. The mitochondrial pyruvate carrier: Has it been unearthed at last?. Cell Metab.. 2012; 16: 141-143 [OpenAIRE] [PubMed] [DOI]

McCommis, KS, Finck, BN. Mitochondrial pyruvate transport: a historical perspective and future research directions. Biochem. J.. 2015; 466: 443-454 [OpenAIRE] [PubMed] [DOI]

Gray, LR, Rauckhorst, AJ, Taylor, EB. A Method for Multiplexed Measurement of Mitochondrial Pyruvate Carrier Activity. J. Biol. Chem. 291, jbc.. 2016; M115: 711663 [OpenAIRE]

Halestrap, AP. The mitochondrial pyruvate carrier. Kinetics and specificity for substrates and inhibitors. Biochem. J.. 1975; 148: 85-96 [OpenAIRE] [PubMed]

46 references, page 1 of 4
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 previous...
Subjects
free text keywords: PROTEÍNAS DA MEMBRANA, PROTEÍNAS DE TRANSPORTE, PARASITOLOGIA, ORGANELAS CELULARES, MITOCÔNDRIAS, AMINOÁCIDOS, TRANSPORTE BIOLÓGICO, TRANSPORTE ATRAVÉS DA MEMBRANA, Article, Multidisciplinary, Glycolysis, Protein secondary structure, Mitochondrial pyruvate carrier 2, Lipid bilayer, Inner mitochondrial membrane, Transporter, Biophysics, Chaperone (protein), biology.protein, biology, Chemistry, Pyruvate transport
Funded by
WT| A laboratory for membrane protein structural biology
Project
  • Funder: Wellcome Trust (WT)
  • Project Code: 202892
  • Funding stream: Molecular Basis of Cell Function
,
WT| The Membrane Protein Laboratory at Diamond Light Source.
Project
  • Funder: Wellcome Trust (WT)
  • Project Code: 099165
  • Funding stream: Cellular and Molecular Neuroscience
46 references, page 1 of 4

Halestrap, AP, Denton, RM. Specific inhibition of pyruvate transport in rat liver mitochondria and human erythrocytes by alpha-cyano-4-hydroxycinnamate. Biochem. J.. 1974; 138: 313-316 [OpenAIRE] [PubMed] [DOI]

Bricker, DK. A mitochondrial pyruvate carrier required for pyruvate uptake in yeast, Drosophila, and humans. Science. 2012; 337: 96-100 [OpenAIRE] [PubMed] [DOI]

Herzig, S. Identification and Functional Expression of the Mitochondrial Pyruvate Carrier. Science (80-.).. 2012; 337: 93-96 [OpenAIRE] [DOI]

Schell, JCC. A Role for the Mitochondrial Pyruvate Carrier as a Repressor of the Warburg Effect and Colon Cancer Cell Growth. Mol. Cell. 2014; 56: 400-413 [OpenAIRE] [PubMed] [DOI]

Vacanti, NMM. Regulation of Substrate Utilization by the Mitochondrial Pyruvate Carrier. Mol. Cell. 2014; 56: 425-435 [OpenAIRE] [PubMed] [DOI]

Bender, T, Pena, G, Martinou, JJ-C. Regulation of mitochondrial pyruvate uptake by alternative pyruvate carrier complexes. EMBO J.. 2015; 34: 1-14 [OpenAIRE] [PubMed] [DOI]

Vigueira, PA. Mitochondrial Pyruvate Carrier 2 Hypomorphism in Mice Leads to Defects in Glucose-Stimulated Insulin Secretion. Cell Rep.. 2014; 7: 2042-2053 [OpenAIRE] [PubMed] [DOI]

8.Vanderperre, B. et al. Embryonic Lethality of Mitochondrial Pyruvate Carrier 1 Deficient Mouse Can Be Rescued by a Ketogenic Diet. PLoS Genet. 12, (2016).

Vanderperre, B, Bender, T, Kunji, ERS, Martinou, JC. Mitochondrial pyruvate import and its effects on homeostasis. Curr. Opin. Cell Biol.. 2015; 33: 35-41 [OpenAIRE] [PubMed] [DOI]

Compan, V. Monitoring Mitochondrial Pyruvate Carrier Activity in Real Time Using a BRET-Based Biosensor: Investigation of the Warburg Effect. Mol. Cell. 2015; 59: 491-501 [OpenAIRE] [PubMed] [DOI]

Liang, L, Li, Q, Huang, L, Li, D, Li, X. Sirt3 binds to and deacetylates mitochondrial pyruvate carrier 1 to enhance its activity. Biochem. Biophys. Res. Commun.. 2015; 468: 807-812 [OpenAIRE] [PubMed] [DOI]

Halestrap, AP. The mitochondrial pyruvate carrier: Has it been unearthed at last?. Cell Metab.. 2012; 16: 141-143 [OpenAIRE] [PubMed] [DOI]

McCommis, KS, Finck, BN. Mitochondrial pyruvate transport: a historical perspective and future research directions. Biochem. J.. 2015; 466: 443-454 [OpenAIRE] [PubMed] [DOI]

Gray, LR, Rauckhorst, AJ, Taylor, EB. A Method for Multiplexed Measurement of Mitochondrial Pyruvate Carrier Activity. J. Biol. Chem. 291, jbc.. 2016; M115: 711663 [OpenAIRE]

Halestrap, AP. The mitochondrial pyruvate carrier. Kinetics and specificity for substrates and inhibitors. Biochem. J.. 1975; 148: 85-96 [OpenAIRE] [PubMed]

46 references, page 1 of 4
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publication . Other literature type . Article . 2018

Human mitochondrial pyruvate carrier 2 as an autonomous membrane transporter

Raghavendra Sashi Krishna Nagampalli; José Edwin Neciosup Quesñay; Douglas Adamoski; Zeyaul Islam; James Birch; Heitor Gobbi Sebinelli; Richard Marcel Bruno Moreira Girard; Carolline Fernanda Rodrigues Ascenção; Angela Maria Fala; Bianca Alves Pauletti; ...