Cited by 173Mitochondrial Function and PathologyMetabolism, Diabetes, and CancerBiochemical Acid Research Studies

The DOI matches its Crossref record; 102 of the 103 references it cites were found in a registry or an index.

The Multifaceted Pyruvate Metabolism: Role of the Mitochondrial Pyruvate Carrier

Open access

Zangari, Joséphine, Petrelli, Francesco, Maillot, Benoît, Martinou, Jean-Claude·2020·Biomolecules

Open this paper in CoChat — free account Open PDF

Abstract

Pyruvate, the end product of glycolysis, plays a major role in cell metabolism. Produced in the cytosol, it is oxidized in the mitochondria where it fuels the citric acid cycle and boosts oxidative phosphorylation. Its sole entry point into mitochondria is through the recently identified mitochondrial pyruvate carrier (MPC). In this review, we report the latest findings on the physiology of the MPC and we discuss how a dysfunctional MPC can lead to diverse pathologies, including neurodegenerative diseases, metabolic disorders, and cancer.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.3390/biom10071068

Cites

102 of 102 references verified0 citation errors · 0 not checkable

Statistics

Figure 1 Metabolic pathways involving mitochondria. In the cytosol, pyruvate is produced through glycolysis, which generates two adenosine triphosphate (ATP) and two reduced nicotinamide adenine dinucleotide (NADH) molecules per molecule of glucose. Pyruvate can also be produced from oxidation of lactate by lactate dehydrogenase (LDH), conversion from alanine by alanine transaminase (ALT), or from malate by cytosolic or mitochondrial malic enzyme (ME). Pyruvate can be imported into mitochondria to be oxidized into acetyl coenzyme A (acetyl-CoA) by the pyruvate dehydrogenase (PDH), which then fuels the tricarboxylic acid (TCA) cycle. Import of pyruvate requires the voltage-dependent anion channel (VDAC) to cross the outer mitochondrial membrane (OMM) and the mitochondrial pyruvate carrier (MPC) to cross the inner mitochondrial membrane (IMM). The TCA cycle can also be fueled by glutamine (Gln) through glutaminolysis or by fatty acids (FA) released from lipid droplets (LD) where they are stored in the form of triglycerides (TG). FAs provide acetyl-CoA through FA β-oxidation. The TCA cycle and β-oxidation both generate the reducing equivalents NADH and flavin adenine dinucleotide (FADH2), which transfer electrons to the electron respiratory chain (ETC), generating more than 30 ATP molecules per molecule of glucose. The last reaction is catalyzed by ATP synthase or Complex V (CV). This process requires the presence of oxygen and is known as oxidative phosphorylation (OXPHOS). In the liver and kidney, pyruvate can be converted into oxaloacetate (OAA) by the pyruvate carboxylase (PC), which is then reduced into malate by the malate dehydrogenase (mMDH). Malate is then exported into the cytosol, converted into OAA by malate dehydrogenase (cMDH) and into phosphoenolpyruvate (PEP) by PEP carboxykinase (PEPCK) and from there into glucose through several steps, including the reversible steps of glycolysis. IMS: intermembrane space; CPT1: carnitine palmitoyltransferase 1; CPT2: carnitine palmitoyltransferase 2; GDH: glutamate dehydrogenase; GLS: glutamase; α-KG: α-ketoglutarate.CC BY · PubMed Central

Figure 2 (A) Semi-SWEET and SWEET motifs. Semi-SWEET is composed of a triple helix bundle in this specific order 1-3-2. SWEET contains two semi-SWEET motifs linked together by a helix. All the helices are crossing the membrane. (B) Model for the topology of MPC1 and MPC2 in the inner mitochondrial membrane (IMM). Here, a semi-SWEET structure is proposed for both MPC1 and MPC2. MA: matrix; IMS: intermembrane space.CC BY · PubMed Central

Figure 3 Tumor cell metabolism. In the primary tumor site, cancer cells mainly rely on aerobic glycolysis (Warburg effect) and this metabolism favors cell proliferation and tumor growth. Some cancer cells escape from the primary tumor site through the bloodstream, generating metastasis in other organs. It is thought that, to do this, some cancer cell types switch to a more oxidative metabolism.CC BY · PubMed Central

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation
Vander Heiden, M. G., Cantley, L. C., & Thompson, C. B. (2009) · Science · doi:10.1126/science.1160809 · Cited by 16,197
On Respiratory Impairment in Cancer Cells
Warburg, O. H. (1956) · Science · doi:10.1126/science.124.3215.269 · Cited by 3,472
Brain energy metabolism: focus on Astrocyte-neuron metabolic cooperation
Bélanger, M., Allaman, I., & Magistretti, P. J. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.08.016 · Cited by 2,313
Skeletal Muscle Insulin Resistance Is the Primary Defect in Type 2 Diabetes
DeFronzo, R. A., & Tripathy, D. (2009) · Diabetes Care · doi:10.2337/dc09-s302 · Cited by 2,102
Oxidative stress, dysfunctional glucose metabolism and Alzheimer disease
Butterfield, D. A., & Halliwell, B. (2019) · Nature Reviews Neuroscience · doi:10.1038/s41583-019-0132-6 · Cited by 1,954
Glucose feeds the TCA cycle via circulating lactate
Hui, S., Ghergurovich, J. M., Morscher, R. J., Jang, C., Teng, X., Lu, W., Esparza, L. A., Reya, T., Zhan, L., Yanxiang Guo, J., et al. (2017) · Nature · doi:10.1038/nature24057 · Cited by 1,721
Lactate Metabolism in Human Lung Tumors
Faubert, B., Li, K. Y., Cai, L., Hensley, C. T., Kim, J., Zacharias, L. G., Yang, C., Do, Q. N., Doucette, S., Burguete, D., et al. (2017) · Cell · doi:10.1016/j.cell.2017.09.019 · Cited by 1,343
Regulation of hepatic glucose metabolism in health and disease
Petersen, M. C., Vatner, D. F., & Shulman, G. I. (2017) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2017.80 · Cited by 1,159
Neuroinflammation in Parkinson's disease: Its role in neuronal death and implications for therapeutic intervention
Tansey, M. G., & Goldberg, M. S. (2010) · Neurobiology of Disease · doi:10.1016/j.nbd.2009.11.004 · Cited by 1,045
Energy metabolism of cancer: Glycolysis versus oxidative phosphorylation (Review)
Zheng, J. (2012) · Oncology Letters · doi:10.3892/ol.2012.928 · Cited by 986
Lactate in the Regulation of Tumor Microenvironment and Therapeutic Approaches
de la Cruz-López, K. G., Castro-Muñoz, L. J., Reyes-Hernández, D. O., García-Carrancá, A., & Manzo-Merino, J. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.01143 · Cited by 940
Exenatide once weekly versus placebo in Parkinson's disease: a randomised, double-blind, placebo-controlled trial
Athauda, D., Maclagan, K., Skene, S. S., Bajwa-Joseph, M., Letchford, D., Chowdhury, K., Hibbert, S., Budnik, N., Zampedri, L., Dickson, J., et al. (2017) · The Lancet · doi:10.1016/s0140-6736(17)31585-4 · Cited by 889
A Mitochondrial Pyruvate Carrier Required for Pyruvate Uptake in Yeast, Drosophila , and Humans
Bricker, D. K., Taylor, E. B., Schell, J. C., Orsak, T., Boutron, A., Chen, Y.-C., Cox, J. E., Cardon, C. M., Van Vranken, J. G., Dephoure, N., et al. (2012) · Science · doi:10.1126/science.1218099 · Cited by 843
Brain metabolism in health, aging, and neurodegeneration
Camandola, S., & Mattson, M. P. (2017) · The EMBO Journal · doi:10.15252/embj.201695810 · Cited by 752
Identification and Functional Expression of the Mitochondrial Pyruvate Carrier
Herzig, S., Raemy, E., Montessuit, S., Veuthey, J.-L., Zamboni, N., Westermann, B., Kunji, E. R. S., & Martinou, J.-C. (2012) · Science · doi:10.1126/science.1218530 · Cited by 747
Self-citation
Regional aerobic glycolysis in the human brain
Vaishnavi, S. N., Vlassenko, A. G., Rundle, M. M., Snyder, A. Z., Mintun, M. A., & Raichle, M. E. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1010459107 · Cited by 738
Glutamine oxidation maintains the TCA cycle and cell survival during impaired mitochondrial pyruvate transport
Yang, C., Ko, B., Hensley, C. T., Jiang, L., Wasti, A. T., Kim, J., Sudderth, J., Calvaruso, M. A., Lumata, L., Mitsche, M., et al. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.09.025 · Cited by 679
Energy Metabolic Phenotype of the Cardiomyocyte During Development, Differentiation, and Postnatal Maturation
Lopaschuk, G. D., & Jaswal, J. S. (2010) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0b013e3181e74a14 · Cited by 636
Insulin regulation of gluconeogenesis
Hatting, M., Tavares, C. D. J., Sharabi, K., Rines, A. K., & Puigserver, P. (2017) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.13435 · Cited by 625
The androgen receptor fuels prostate cancer by regulating central metabolism and biosynthesis
Massie, C. E., Lynch, A., Ramos‐Montoya, A., Boren, J., Stark, R., Fazli, L., Warren, A., Scott, H., Madhu, B., Sharma, N., et al. (2011) · The EMBO Journal · doi:10.1038/emboj.2011.158 · Cited by 624
A Mitochondrial Switch Promotes Tumor Metastasis
Porporato, P. E., Payen, V. L., Pérez‐Escuredo, J., Saedeleer, C. J. D., Danhier, P., Copetti, T., Dhup, S., Tardy, M., Vazeille, T., Bouzin, C., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.06.043 · Cited by 571
Metabolic Signaling in Fuel-Induced Insulin Secretion
Prentki, M., Matschinsky, F. M., & Madiraju, S. R. M. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.05.018 · Cited by 548
Exenatide and the treatment of patients with Parkinson's disease
Aviles-Olmos, I., Dickson, J., Kefalopoulou, Z., Djamshidian, A., Ell, P., Soderlund, T., Whitton, P., Wyse, R., Isaacs, T., Lees, A., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci68295 · Cited by 529
A Role for the Mitochondrial Pyruvate Carrier as a Repressor of the Warburg Effect and Colon Cancer Cell Growth
Schell, J. C., Olson, K. A., Jiang, L., Hawkins, A. J., Van Vranken, J. G., Xie, J., Egnatchik, R. A., Earl, E. G., DeBerardinis, R. J., & Rutter, J. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.09.026 · Cited by 363
Triggers, Facilitators, and Aggravators: Redefining Parkinson’s Disease Pathogenesis
Johnson, M., Stecher, B., Labrie, V., Brundin, L., & Brundin, P. (2018) · Trends in Neurosciences · doi:10.1016/j.tins.2018.09.007 · Cited by 320
Thiazolidinediones are acute, specific inhibitors of the mitochondrial pyruvate carrier
Divakaruni, A. S., Wiley, S. E., Rogers, G. W., Andreyev, A. Y., Petrosyan, S., Loviscach, M., Wall, E. A., Yadava, N., Heuck, A. P., Ferrick, D. A., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1303360110 · Cited by 308
Motor and Cognitive Advantages Persist 12 Months After Exenatide Exposure in Parkinson’s Disease
Avilés-Olmos, I., Dickson, J. C., Kefalopoulou, Z. M., Djamshidian, A., Kahan, J., Ell, P. J., Whitton, P. S., Wyse, R. K. H., Isaacs, T., Lees, A. J., et al. (2014) · Journal of Parkinson s Disease · doi:10.3233/jpd-140364 · Cited by 300
Regulation of Substrate Utilization by the Mitochondrial Pyruvate Carrier
Vacanti, N. M., Divakaruni, A. S., Green, C. R., Parker, S. J., Henry, R. R., Ciaraldi, T. P., Murphy, A. N., & Metallo, C. M. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.09.024 · Cited by 277
Metabolic cycling in control of glucose-stimulated insulin secretion
Jensen, M. V., Joseph, J. W., Ronnebaum, S. M., Burgess, S. C., Sherry, A. D., & Newgard, C. B. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90604.2008 · Cited by 259
Pyruvate-Carboxylase-Mediated Anaplerosis Promotes Antioxidant Capacity by Sustaining TCA Cycle and Redox Metabolism in Liver
Cappel, D. A., Deja, S., Duarte, J. A. G., Kucejova, B., Iñigo, M., Fletcher, J. A., Fu, X., Berglund, E. D., Liu, T., Elmquist, J. K., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.03.014 · Cited by 242
Hepatic Mitochondrial Pyruvate Carrier 1 Is Required for Efficient Regulation of Gluconeogenesis and Whole-Body Glucose Homeostasis
Gray, L. R., Sultana, M. R., Rauckhorst, A. J., Oonthonpan, L., Tompkins, S. C., Sharma, A., Fu, X., Miao, R., Pewa, A. D., Brown, K., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.07.027 · Cited by 218
Loss of Mitochondrial Pyruvate Carrier 2 in the Liver Leads to Defects in Gluconeogenesis and Compensation via Pyruvate-Alanine Cycling
McCommis, K. S., Chen, Z., Fu, X., McDonald, W. G., Colca, J. R., Kletzien, R. F., Burgess, S. C., & Finck, B. N. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.07.028 · Cited by 211
Insulin sensitizer MSDC-0602K in non-alcoholic steatohepatitis: a randomized, double-blind, placebo-controlled phase IIb study
Harrison, S. A., Alkhouri, N., Davison, B. A., Sanyal, A., Edwards, C., Colca, J. R., Lee, B. H., Loomba, R., Cusi, K., Kolterman, O., et al. (2020) · Journal of Hepatology · doi:10.1016/j.jhep.2019.10.023 · Cited by 211
Wild-Type p53 Promotes Cancer Metabolic Switch by Inducing PUMA-Dependent Suppression of Oxidative Phosphorylation
Kim, J., Yu, L., Chen, W., Xu, Y., Wu, M., Todorova, D., Tang, Q., Feng, B., Jiang, L., Chen, G., et al. (2019) · Cancer Cell · doi:10.1016/j.ccell.2018.12.012 · Cited by 205
Metabolic profiling of Parkinson's disease: evidence of biomarker from gene expression analysis and rapid neural network detection
Ahmed, S. S. S. J., Santosh, W., Kumar, S., & Christlet, H. T. T. (2009) · Journal of Biomedical Science · doi:10.1186/1423-0127-16-63 · Cited by 197
Mitochondrial pyruvate carrier regulates autophagy, inflammation, and neurodegeneration in experimental models of Parkinson’s disease
Ghosh, A., Tyson, T., George, S., Hildebrandt, E. N., Steiner, J. A., Madaj, Z., Schulz, E., Machiela, E., McDonald, W. G., Galvis, M. L. E., et al. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aag2210 · Cited by 193
Heptahelical protein PQLC2 is a lysosomal cationic amino acid exporter underlying the action of cysteamine in cystinosis therapy
Jézégou, A., Llinares, E., Anne, C., Kieffer‐Jaquinod, S., O’Regan, S., Aupetit, J., Chabli, A., Sagné, C., Debacker, C., Chadefaux, B., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1211198109 · Cited by 192
Interruption of lactate uptake by inhibiting mitochondrial pyruvate transport unravels direct antitumor and radiosensitizing effects
Corbet, C., Bastien, E., Draoui, N., Doix, B., Mignion, L., Jordan, B. F., Marchand, A., Vanherck, J., Chaltin, P., Schakman, O., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03525-0 · Cited by 189
The role of glycolysis and mitochondrial respiration in the formation and functioning of endothelial tip cells during angiogenesis
Yetkin-Arik, B., Vogels, I. M. C., Nowak-Sliwinska, P. M., Weiss, A., Houtkooper, R. H., Noorden, C. J. F. V., Klaassen, I., & Schlingemann, R. O. (2019) · Scientific Reports · doi:10.1038/s41598-019-48676-2 · Cited by 189
Structure and function of SemiSWEET and SWEET sugar transporters
Feng, L., & Frommer, W. B. (2015) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2015.05.005 · Cited by 173
Regulation of Tumor Initiation by the Mitochondrial Pyruvate Carrier
Bensard, C., Wisidagama, D. R., Olson, K. A., Berg, J. A., Krah, N. M., Schell, J. C., Nowinski, S. M., Fogarty, S., Bott, A. J., Wei, P., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.11.002 · Cited by 170
Inhibition of the mitochondrial pyruvate carrier protects from excitotoxic neuronal death
Divakaruni, A. S., Wallace, M., Buren, C., Martyniuk, K. M., Andreyev, A. Y., Li, E., Fields, J. A., Cordes, T., Reynolds, I. J., Bloodgood, B. L., et al. (2017) · The Journal of Cell Biology · doi:10.1083/jcb.201612067 · Cited by 169
Mitochondrial pyruvate import is a metabolic vulnerability in androgen receptor-driven prostate cancer
Bader, D. A., Hartig, S. M., Putluri, V., Foley, C., Hamilton, M. P., Smith, E. A., Saha, P., Panigrahi, A., Walker, C. M., Zong, L., et al. (2018) · Nature Metabolism · doi:10.1038/s42255-018-0002-y · Cited by 168
The transport of pyruvate in rat liver mitochondria
Papa, S., Francavilla, A., Paradies, G., & Meduri, B. (1971) · FEBS Letters · doi:10.1016/0014-5793(71)80200-4 · Cited by 166
Glucose metabolism in nerve terminals
Ashrafi, G., & Ryan, T. A. (2017) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2017.03.007 · Cited by 151
Targeting the mitochondrial pyruvate carrier attenuates fibrosis in a mouse model of nonalcoholic steatohepatitis
McCommis, K. S., Hodges, W. T., Brunt, E. M., Nalbantoglu, I., McDonald, W. G., Holley, C. L., Fujiwara, H., Schaffer, J. E., Colca, J. R., & Finck, B. N. (2016) · Hepatology · doi:10.1002/hep.29025 · Cited by 139
Regulation of mitochondrial pyruvate uptake by alternative pyruvate carrier complexes
Bender, T., Pena, G., & Martinou, J. (2015) · The EMBO Journal · doi:10.15252/embj.201490197 · Cited by 134
Self-citation
Glitazone Treatment and Incidence of Parkinson’s Disease among People with Diabetes: A Retrospective Cohort Study
Brauer, R., Bhaskaran, K., Chaturvedi, N., Dexter, D. T., Smeeth, L. L., & Douglas, I. (2015) · PLoS Medicine · doi:10.1371/journal.pmed.1001854 · Cited by 130
Defective Mitochondrial Pyruvate Flux Affects Cell Bioenergetics in Alzheimer’s Disease-Related Models
Rossi, A., Rigotto, G., Valente, G., Giorgio, V., Basso, E., Filadi, R., & Pizzo, P. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.01.060 · Cited by 109
Glitazone use associated with reduced risk of Parkinson's disease
Brakedal, B., Flønes, I. H., Reiter, S. F., Torkildsen, Ø., Dölle, C., Aßmus, J., Haugarvoll, K., & Tzoulis, C. (2017) · Movement Disorders · doi:10.1002/mds.27128 · Cited by 108
Engrailed homeoprotein blocks degeneration in adult dopaminergic neurons through LINE‐1 repression
de Thé, F.-X. B., Rekaik, H., Pezé-Heidsieck, E., Massiani-Beaudoin, O., Joshi, R. L., Fuchs, J., & Prochiantz, A. (2018) · The EMBO Journal · doi:10.15252/embj.201797374 · Cited by 104
Mitochondrial Pyruvate Carrier 2 Hypomorphism in Mice Leads to Defects in Glucose-Stimulated Insulin Secretion
Vigueira, P. A., McCommis, K. S., Schweitzer, G. G., Remedi, M. S., Chambers, K. T., Fu, X., McDonald, W. G., Cole, S. L., Colca, J. R., Kletzien, R. F., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.05.017 · Cited by 103
Loss of MPC1 reprograms retinal metabolism to impair visual function
Grenell, A., Wang, Y., Yam, M., Swarup, A., Dilan, T. L., Hauer, A., Linton, J. D., Philp, N. J., Gregor, E., Zhu, S., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1812941116 · Cited by 101
Mitochondrial metabolism of pyruvate is essential for regulating glucose-stimulated insulin secretion
Patterson, J. N., Cousteils, K., Lou, J. W., Manning Fox, J. E., MacDonald, P. E., & Joseph, J. W. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.521666 · Cited by 98
Monitoring Mitochondrial Pyruvate Carrier Activity in Real Time Using a BRET-Based Biosensor: Investigation of the Warburg Effect
Compan, V., Pierredon, S., Vanderperre, B., Krznar, P., Marchiq, I., Zamboni, N., Pouysségur, J., & Martinou, J. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.06.035 · Cited by 92
Self-citation
Impaired mitochondrial pyruvate importation in a patient and a fetus at risk
Brivet, M. (2003) · Molecular Genetics and Metabolism · doi:10.1016/s1096-7192(03)00016-7 · Cited by 92
Application of mitochondrial pyruvate carrier blocker UK5099 creates metabolic reprogram and greater stem-like properties in LnCap prostate cancer cells in vitro
Zhong, Y., Li, X., Yu, D., Li, X., Li, Y., Long, Y., Yuan, Y., Ji, Z., Zhang, M., Wen, J., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.5386 · Cited by 85
Disrupting Mitochondrial Pyruvate Uptake Directs Glutamine into the TCA Cycle away from Glutathione Synthesis and Impairs Hepatocellular Tumorigenesis
Tompkins, S. C., Sheldon, R. D., Rauckhorst, A. J., Noterman, M. F., Solst, S. R., Buchanan, J. L., Mapuskar, K. A., Pewa, A. D., Gray, L. R., Oonthonpan, L., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.07.098 · Cited by 79
What Effects Might Exenatide have on Non-Motor Symptoms in Parkinson’s Disease: A Post Hoc Analysis
Athauda, D. S., Maclagan, K., Budnik, N., Zampedri, L., Hibbert, S., Skene, S. S., Chowdhury, K., Avilés-Olmos, I., Limousin, P. D., & Foltynie, T. (2018) · Journal of Parkinson s Disease · doi:10.3233/jpd-181329 · Cited by 79
Mitochondrial pyruvate carrier function determines cell stemness and metabolic reprogramming in cancer cells
Li, X., Han, G., Li, X., Kan, Q., Fan, Z., Li, Y., Ji, Y., Zhao, J., Zhang, M., Grigalavicius, M., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.18199 · Cited by 78
PGC1α promotes cholangiocarcinoma metastasis by upregulating PDHA1 and MPC1 expression to reverse the Warburg effect
Li, D., Wang, C., Ma, P., Yu, Q., Gu, M., Dong, L., Jiang, W., Pan, S., Xie, C., Han, J., et al. (2018) · Cell Death and Disease · doi:10.1038/s41419-018-0494-0 · Cited by 77
The mitochondrial pyruvate carrier mediates high fat diet-induced increases in hepatic TCA cycle capacity
Rauckhorst, A. J., Gray, L. R., Sheldon, R. D., Fu, X., Pewa, A. D., Feddersen, C. R., Dupuy, A. J., Gibson-Corley, K. N., Cox, J. E., Burgess, S. C., et al. (2017) · Molecular Metabolism · doi:10.1016/j.molmet.2017.09.002 · Cited by 74
The yeast mitochondrial pyruvate carrier is a hetero-dimer in its functional state
Tavoulari, S., Thangaratnarajah, C., Mavridou, V., Harbour, M. E., Martinou, J., & Kunji, E. R. (2019) · The EMBO Journal · doi:10.15252/embj.2018100785 · Cited by 73
Self-citation
Mitochondrial pyruvate and fatty acid flux modulate MICU1-dependent control of MCU activity
Nemani, N., Dong, Z., Daw, C. C., Madaris, T. R., Karthik, R., Enslow, B. T., Rubannelsonkumar, C. S., Shanmughapriya, S., Mallireddigari, V., Maity, S., et al. (2020) · Science Signaling · doi:10.1126/scisignal.aaz6206 · Cited by 71
Impaired skeletal muscle mitochondrial pyruvate uptake rewires glucose metabolism to drive whole-body leanness
Sharma, A., Oonthonpan, L., Sheldon, R. D., Rauckhorst, A. J., Zhu, Z., Tompkins, S. C., Cho, K., Grzesik, W. J., Gray, L. R., Scerbo, D. A., et al. (2019) · eLife · doi:10.7554/elife.45873 · Cited by 68
Bioenergetics failure in neurodegenerative diseases: back to the future
Saxena, U. (2012) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2012.664135 · Cited by 67
Embryonic Lethality of Mitochondrial Pyruvate Carrier 1 Deficient Mouse Can Be Rescued by a Ketogenic Diet
Vanderperre, B., Herzig, S., Krznar, P., Hörl, M., Ammar, Z., Montessuit, S., Pierredon, S., Zamboni, N., & Martinou, J. (2016) · PLoS Genetics · doi:10.1371/journal.pgen.1006056 · Cited by 67
Self-citation
Decreased Mitochondrial Pyruvate Transport Activity in the Diabetic Heart
Vadvalkar, S. S., Matsuzaki, S., Eyster, C. A., Giorgione, J. R., Bockus, L. B., Kinter, C. S., Kinter, M. T., & Humphries, K. M. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.753509 · Cited by 63
The pyruvate carboxylase-pyruvate dehydrogenase axis in islet pyruvate metabolism: Going round in circles?
Sugden, M. C., & Holness, M. J. (2011) · Islets · doi:10.4161/isl.3.6.17806 · Cited by 60
Fatty Acid Oxidation Promotes Cardiomyocyte Proliferation Rate but Does Not Change Cardiomyocyte Number in Infant Mice
Cao, T., Liccardo, D., LaCanna, R., Zhang, X., Lü, R., Finck, B. N., Leigh, T., Chen, X., Drosatos, K., & Tian, Y. (2019) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2019.00042 · Cited by 60
An Evaluation of MSDC-0160, A Prototype mTOT Modulating Insulin Sensitizer, in Patients with Mild Alzheimer’s Disease
Shah, R. C., Matthews, D. C., Andrews, R. D., Capuano, A. W., Fleischman, D. A., VanderLugt, J. T., & Colca, J. R. (2014) · Current Alzheimer Research · doi:10.2174/1567205011666140616113406 · Cited by 58
MPC1, a key gene in cancer metabolism, is regulated by COUPTFII in human prostate cancer
Wang, L., Xu, M., Qin, J., Lin, S., Lee, H.-J., Tsai, S. Y., & Tsai, M. (2016) · Oncotarget · doi:10.18632/oncotarget.7405 · Cited by 58
Sirt3 binds to and deacetylates mitochondrial pyruvate carrier 1 to enhance its activity
Liang, L., Li, Q., Huang, L., Li, D., & Li, X. (2015) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2015.11.036 · Cited by 56
A novel KDM5A/MPC-1 signaling pathway promotes pancreatic cancer progression via redirecting mitochondrial pyruvate metabolism
Cui, J., Quan, M., Xie, D., Gao, Y., Guha, S., Fallon, M. B., Chen, J., & Xie, K. (2020) · Oncogene · doi:10.1038/s41388-019-1051-8 · Cited by 55
Human mitochondrial pyruvate carrier 2 as an autonomous membrane transporter
Nagampalli, R. S. K., Quesñay, J. E. N., Adamóski, D., Islam, Z., Birch, J., Sebinelli, H. G., Girard, R. M. B. M., Ascenção, C. F. R., Fala, A. M., Pauletti, B. A., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-21740-z · Cited by 53
Requirement for the Mitochondrial Pyruvate Carrier in Mammalian Development Revealed by a Hypomorphic Allelic Series
Bowman, C. E., Zhao, L., Härtung, T., & Wolfgang, M. J. (2016) · Molecular and Cellular Biology · doi:10.1128/mcb.00166-16 · Cited by 52
MPC1-like Is a Placental Mammal-specific Mitochondrial Pyruvate Carrier Subunit Expressed in Postmeiotic Male Germ Cells
Vanderperre, B., Cermakova, K., Escoffier, J., Kaba, M., Bender, T., Nef, S., & Martinou, J. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.733840 · Cited by 52
Self-citation
Differential Regulation of Mitochondrial Pyruvate Carrier Genes Modulates Respiratory Capacity and Stress Tolerance in Yeast
Timón‐Gómez, A., Proft, M., & Pascual‐Ahuir, A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0079405 · Cited by 51
Mitochondrial pyruvate carrier 1 expression controls cancer epithelial‐mesenchymal transition and radioresistance
Takaoka, Y., Konno, M., Koseki, J., Colvin, H. S., Asai, A., Tamari, K., Satoh, T., Mori, M., Doki, Y., Ogawa, K., et al. (2019) · Cancer Science · doi:10.1111/cas.13980 · Cited by 49
Inhibition of ERRα Prevents Mitochondrial Pyruvate Uptake Exposing NADPH-Generating Pathways as Targetable Vulnerabilities in Breast Cancer
Park, S. H., Safi, R., Liu, X., Baldi, R. M., Liu, W., Liu, J., Locasale, J. W., Chang, C., & McDonnell, D. P. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.05.066 · Cited by 48
MPC1 and MPC2 expressions are associated with favorable clinical outcomes in prostate cancer
Li, X., Ji, Y., Han, G., Li, X., Fan, Z., Li, Y., Zhong, Y., Cao, J., Zhao, J., Zhang, M., et al. (2016) · BMC Cancer · doi:10.1186/s12885-016-2941-6 · Cited by 47
An ancestral role for the mitochondrial pyruvate carrier in glucose-stimulated insulin secretion
McCommis, K. S., Hodges, W. T., Bricker, D. K., Wisidagama, D. R., Compan, V., Remedi, M. S., Thummel, C. S., & Finck, B. N. (2016) · Molecular Metabolism · doi:10.1016/j.molmet.2016.06.016 · Cited by 44
Defining the Substrate Spectrum of the TIM22 Complex Identifies Pyruvate Carrier Subunits as Unconventional Cargos
Gomkale, R., Cruz‐Zaragoza, L. D., Suppanz, I., Guiard, B., Montoya, J., Callegari, S., Pacheu‐Grau, D., Warscheid, B., & Rehling, P. (2020) · Current Biology · doi:10.1016/j.cub.2020.01.024 · Cited by 42
Mitochondrial pyruvate carrier function is negatively linked to Warburg phenotype in vitro and malignant features in esophageal squamous cell carcinomas
Li, Y., Li, X., Kan, Q., Zhang, M., Li, X., Xu, R., Wang, J., Yu, D., Goscinski, M. A., Wen, J., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.13717 · Cited by 41
Thiazolidinediones and Parkinson Disease: A Cohort Study
Connolly, J. G., Bykov, K., & Gagne, J. J. (2015) · American Journal of Epidemiology · doi:10.1093/aje/kwv109 · Cited by 39
Treating Hepatic Steatosis and Fibrosis by Modulating Mitochondrial Pyruvate Metabolism
McCommis, K. S., & Finck, B. N. (2019) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2018.09.017 · Cited by 39
The mitochondrial carrier pathway transports non-canonical substrates with an odd number of transmembrane segments
Rampelt, H., Sučec, I., Bersch, B., Horten, P., Perschil, I., Martinou, J., van der Laan, M., Wiedemann, N., Schanda, P., & Pfanner, N. (2020) · BMC Biology · doi:10.1186/s12915-019-0733-6 · Cited by 37
Self-citation
MPC1 is essential for PGC-1α-induced mitochondrial respiration and biogenesis
Koh, E., Kim, Y. K., Shin, D., & Kim, K. (2018) · Biochemical Journal · doi:10.1042/bcj20170967 · Cited by 36
Mitochondrial pyruvate carrier 1 functions as a tumor suppressor and predicts the prognosis of human renal cell carcinoma
Tang, X., Chen, Q., Li, Y., Wang, Y., Zou, H., Fu, W., Niu, Q., Pan, Q., Jiang, P., Xu, X., et al. (2018) · Laboratory Investigation · doi:10.1038/s41374-018-0138-0 · Cited by 36
MPC1 deletion is associated with poor prognosis and temozolomide resistance in glioblastoma
Chai, Y., Wang, C., Liu, W., Fan, Y., & Zhang, Y. (2019) · Journal of Neuro-Oncology · doi:10.1007/s11060-019-03226-8 · Cited by 35
MPC1 deficiency accelerates lung adenocarcinoma progression through the STAT3 pathway
Zou, H., Chen, Q., Zhang, A., Wang, S., Wu, H., Yuan, Y., Wang, S., Yu, J. H., Luo, M., Wen, X., et al. (2019) · Cell Death and Disease · doi:10.1038/s41419-019-1324-8 · Cited by 34
Two human patient mitochondrial pyruvate carrier mutations reveal distinct molecular mechanisms of dysfunction
Oonthonpan, L., Rauckhorst, A. J., Gray, L. R., Boutron, A., & Taylor, E. B. (2019) · JCI Insight · doi:10.1172/jci.insight.126132 · Cited by 31
Artemether ameliorates type 2 diabetic kidney disease by increasing mitochondrial pyruvate carrier content in db/db mice.
Han, P., Wang, Y., Zhan, H., Weng, W., Yu, X., Ge, N., Wang, W., Song, G., Yi, T., Li, S., et al. (2019) · Europe PMC (PubMed Central) · Cited by 29
Causes of upregulation of glycolysis in lymphocytes upon stimulation. A comparison with other cell types
Stark, H., Fichtner, M., König, R., Lorkowski, S., & Schuster, S. (2015) · Biochimie · doi:10.1016/j.biochi.2015.09.017 · Cited by 23
Establishment of mitochondrial pyruvate carrier 1 (MPC1) gene knockout mice with preliminary gene function analyses
Li, X., Li, Y., Han, G., Li, X., Ji, Y., Fan, Z., Zhong, Y., Cao, J., Zhao, J., Goscinski, M. A., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.13210 · Cited by 23
Enhanced mitochondrial pyruvate transport elicits a robust ROS production to sensitize the antitumor efficacy of interferon-γ in colon cancer
Tai, Y., Cao, F., Li, M., Li, P., Xu, T., Wang, X., Yu, Y., Gu, B., Yu, X., Cai, X., et al. (2018) · Redox Biology · doi:10.1016/j.redox.2018.10.024 · Cited by 23
Mitochondrial pyruvate carrier modulates the epithelial-mesenchymal transition in cholangiocarcinoma
Ohashi, T., Eguchi, H., Kawamoto, K., Konno, M., Asai, A., Colvin, H. S., Ueda, Y., Takaoka, H., Iwagami, Y., Yamada, D., et al. (2017) · Oncology Reports · doi:10.3892/or.2017.6172 · Cited by 18
Expansion of the Transporter-Opsin-G protein-coupled receptor superfamily with five new protein families
Medrano-Soto, A., Ghazi, F., Hendargo, K. J., Moreno‐Hagelsieb, G., Myers, S., & Saier, M. H. (2020) · PLoS ONE · doi:10.1371/journal.pone.0231085 · Cited by 18
Characteristic Analysis of Homo- and Heterodimeric Complexes of Human Mitochondrial Pyruvate Carrier Related to Metabolic Diseases
Lee, J., Jin, Z., Lee, D., Yun, J.-H., & Lee, W. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21093403 · Cited by 18
MSDC-0160 and MSDC-0602 Binding with Human Mitochondrial Pyruvate Carrier (MPC) 1 and 2 Heterodimer
Phelix, C. F., Bourdon, A. K., Dugan, J. L., Villareal, G., & Perry, G. L. (2017) · International Journal of Knowledge Discovery in Bioinformatics · doi:10.4018/ijkdb.2017070103 · Cited by 8
Mitochondrial Pyruvate Carrier 1 and 2 Heterodimer, In Silico, Models of Plant and Human Complexes
Dugan, J. L., Bourdon, A. K., & Phelix, C. F. (2017) · International Journal of Knowledge Discovery in Bioinformatics · doi:10.4018/ijkdb.2017070102 · Cited by 7
Alzheimer's and Parkinson's Disease Novel Therapeutic Target
Bourdon, A. K., Villareal, G., Perry, G. L., & Phelix, C. F. (2017) · International Journal of Knowledge Discovery in Bioinformatics · doi:10.4018/ijkdb.2017070104 · Cited by 4

Sorted by citations

Energy metabolism in health and diseases
Liu, H., Wang, S., Wang, J., Guo, X., Song, Y., Fu, K., Gao, Z., Liu, D., He, W., & Yang, L. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02141-x · Cited by 484
Tunneling nanotubes, TNT, communicate glioblastoma with surrounding non-tumor astrocytes to adapt them to hypoxic and metabolic tumor conditions
Valdebenito, S., Malik, S., Luu, R. H., Loudig, O. D., Mitchell, M. I., Okafo, G. N., Bhat, K., Prideaux, B., & Eugenín, E. A. (2021) · Scientific Reports · doi:10.1038/s41598-021-93775-8 · Cited by 120
Mitochondrial pyruvate metabolism regulates the activation of quiescent adult neural stem cells
Petrelli, F., Scandella, V., Montessuit, S., Zamboni, N., Martinou, J., & Knobloch, M. (2023) · Science Advances · doi:10.1126/sciadv.add5220 · Cited by 89
Self-citation
Effects of Metabolism on Macrophage Polarization Under Different Disease Backgrounds
Sun, J., Xu, X., & Jin, L. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.880286 · Cited by 81
Cancer cell metabolism: Rewiring the mitochondrial hub
Oliveira, G. L., Coelho, A. R., Marques, R., & Oliveira, P. J. (2020) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2020.166016 · Cited by 65

See all 173

Authors: Zangari, J., Petrelli, F., Maillot, B., & Martinou, J.-C.
Affiliations: University of Geneva (CH)
Corresponding author: Martinou, Jean-Claude
ORCID: Zangari, Joséphine
Petrelli, Francesco
Martinou, Jean-Claude
Venue: Biomolecules
Publisher: MDPI AG
Published: 2020-07-17
Volume: 10
Issue: 7
Pages: 1068
ISSN: 2218-273X (ISSN-L)
DOI: 10.3390/biom10071068
PMC: PMC7407832
OpenAlex: W3042494222
Cited by: 172
References: 103
Citations by year: 2026: 33 · 2025: 47 · 2024: 33 · 2023: 30 · 2022: 16 · 2021: 11 · 2020: 2
FWCI: 1.44
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: Biomolecules (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: Oncosuisse (KFS-4434-02-2018)
Swiss National Foundation (31003A_179421)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Biochemical Acid Research Studies
Keywords: pyruvate metabolism, mitochondrial pyruvate carrier, glycolysis, TCA cycle, oxidative phosphorylation, mitochondrial dysfunction, neurodegenerative diseases, metabolic disorders, cancer
MeSH terms: Animals, Gene Expression Regulation, Humans, Metabolic Diseases, Mitochondria, Neoplasms, Pyruvic Acid, Neurodegenerative Diseases, Monocarboxylic Acid Transporters, Mitochondrial Membrane Transport Proteins

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

The Multifaceted Pyruvate Metabolism: Role of the Mitochondrial Pyruvate Carrier

Abstract

Overview

Integrity signals

Figures

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks