ArticlePLoS genetics2016
Embryonic Lethality of Mitochondrial Pyruvate Carrier 1 Deficient Mouse Can Be Rescued by a Ketogenic Diet.
Article in PLoS genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 65 citations in OpenAlex.
- Polymorphisms inAnimals : an open access journal from MDPI · 2026Article
- TruncatingbioRxiv : the preprint server for biology · 2026Article
- Mitochondrial CaBiomolecules · 2026Review
- ALDH4A1 functions as an active component of the MPC complex maintaining mitochondrial pyruvate import for TCA cycle entry and tumour suppression.Nature cell biology · 2025Article
- Computational structural prediction and chemical inhibition of the human mitochondrial pyruvate carrier protein heterodimer complex.bioRxiv : the preprint server for biology · 2024Article
- Mitochondrial pyruvate metabolism and glutaminolysis toggle steady-state and emergency myelopoiesis.The Journal of experimental medicine · 2023Article
- Fifty years of the mitochondrial pyruvate carrier: New insights into its structure, function, and inhibition.Acta physiologica (Oxford, England) · 2023Review
- The Hepatic Mitochondrial Pyruvate Carrier as a Regulator of Systemic Metabolism and a Therapeutic Target for Treating Metabolic Disease.Biomolecules · 2023Review
- Ketogenic Diet Treatment of Defects in the Mitochondrial Malate Aspartate Shuttle and Pyruvate Carrier.Nutrients · 2022Article
- The mitochondrial pyruvate carrier at the crossroads of intermediary metabolism.American journal of physiology. Endocrinology and metabolism · 2022Review
- Paradoxical neuronal hyperexcitability in a mouse model of mitochondrial pyruvate import deficiency.eLife · 2022Article
- AGC1 Deficiency: Pathology and Molecular and Cellular Mechanisms of the Disease.International journal of molecular sciences · 2022Review
- The mitochondrial pyruvate carrier (MPC) complex mediates one of three pyruvate-supplying pathways that sustain Arabidopsis respiratory metabolism.The Plant cell · 2021Article
- Playing with Pyr: alternate sources of mitochondrial pyruvate fuel plant respiration.The Plant cell · 2021Article
- Energy Metabolism of Osteocytes.Current osteoporosis reports · 2021Review
- Metabolic reprogramming of terminally exhausted CD8Nature immunology · 2021Article
- Heart failure-emerging roles for the mitochondrial pyruvate carrier.Cell death and differentiation · 2021Review
- Regulation of maternal-fetal metabolic communication.Cellular and molecular life sciences : CMLS · 2021Review
- Blocking mitochondrial pyruvate import in brown adipocytes induces energy wasting via lipid cycling.EMBO reports · 2020Article
- The Role of Pi, Glutamine and the Essential Amino Acids in Modulating the Metabolism in Diabetes and Cancer.Journal of diabetes and metabolic disorders · 2020Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitochondrial import of pyruvate by the mitochondrial pyruvate carrier (MPC) is a central step which links cytosolic and mitochondrial intermediary metabolism. To investigate the role of the MPC in mammalian physiology and development, we generated a mouse strain with complete loss of MPC1 expression. This resulted in embryonic lethality at around E13.5. Mouse embryonic fibroblasts (MEFs) derived from mutant mice displayed defective pyruvate-driven respiration as well as perturbed metabolic profiles, and both defects could be restored by reexpression of MPC1. Labeling experiments using 13C-labeled glucose and glutamine demonstrated that MPC deficiency causes increased glutaminolysis and reduced contribution of glucose-derived pyruvate to the TCA cycle. Morphological defects were observed in mutant embryonic brains, together with major alterations of their metabolome including lactic acidosis, diminished TCA cycle intermediates, energy deficit and a perturbed balance of neurotransmitters. Strikingly, these changes were reversed when the pregnant dams were fed a ketogenic diet, which provides acetyl-CoA directly to the TCA cycle and bypasses the need for a functional MPC. This allowed the normal gestation and development of MPC deficient pups, even though they all died within a few minutes post-delivery. This study establishes the MPC as a key player in regulating the metabolic state necessary for embryonic development, neurotransmitter balance and post-natal survival.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.