Evidence map›Paper›PMID 27215380›Full record

ArticleMolecular and cellular biology2016

Requirement for the Mitochondrial Pyruvate Carrier in Mammalian Development Revealed by a Hypomorphic Allelic Series.

Caitlyn E Bowman, Liang Zhao, Thomas Hartung, Michael J Wolfgang

Open access · bronzeAbstract read
In one paragraph

Article in Molecular and cellular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
2.8field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

37 citing papers in PubMed, 58 citations in OpenAlex.

  1. TruncatingbioRxiv : the preprint server for biology · 2026
    Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Review
  12. The mitochondrial pyruvate carrier at the crossroads of intermediary metabolism.American journal of physiology. Endocrinology and metabolism · 2022
    Review
  13. Article
  14. Chromatin as a sensor of metabolic changes during early development.Frontiers in cell and developmental biology · 2022
    Review
  15. Review
  16. Regulation of maternal-fetal metabolic communication.Cellular and molecular life sciences : CMLS · 2021
    Review
  17. Article
  18. Article
  19. Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Caitlyn E BowmanDepartment of Biological Chemistry and Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Liang ZhaoDepartment of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.ORCID 0000-0002-2126-6778
Thomas HartungDepartment of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
Michael J WolfgangDepartment of Biological Chemistry and Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA mwolfga1@jhmi.edu.
Johns Hopkins University · US

Funding

BIOCHEMISTRY, CELLULAR AND MOLECULAR BIOLOGY PROGRAMT32GM007445 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI GREEN, RACHEL · 1985 to 2021
$24.1M
Regulation of Neuronal Lipid Homeostasis By ThioesterasesR01NS072241 · NINDS · JOHNS HOPKINS UNIVERSITY · PI WOLFGANG, MICHAEL J. · 2011 to 2020
$4.0M
NIGMS NIH HHS T32 GM007445NINDS NIH HHS R01 NS072241
6 · The paper itself

Abstract

Glucose and oxygen are two of the most important molecules transferred from mother to fetus during eutherian pregnancy, and the metabolic fates of these nutrients converge at the transport and metabolism of pyruvate in mitochondria. Pyruvate enters the mitochondrial matrix through the mitochondrial pyruvate carrier (MPC), a complex in the inner mitochondrial membrane that consists of two essential components, MPC1 and MPC2. Here, we define the requirement for mitochondrial pyruvate metabolism during development with a progressive allelic series of Mpc1 deficiency in mouse. Mpc1 deletion was homozygous lethal in midgestation, but Mpc1 hypomorphs and tissue-specific deletion of Mpc1 presented as early perinatal lethality. The allelic series demonstrated that graded suppression of MPC resulted in dose-dependent metabolic and transcriptional changes. Steady-state metabolomics analysis of brain and liver from Mpc1 hypomorphic embryos identified compensatory changes in amino acid and lipid metabolism. Flux assays in Mpc1-deficient embryonic fibroblasts also reflected these changes, including a dramatic increase in mitochondrial alanine utilization. The mitochondrial alanine transaminase GPT2 was found to be necessary and sufficient for increased alanine flux upon MPC inhibition. These data show that impaired mitochondrial pyruvate transport results in biosynthetic deficiencies that can be mitigated in part by alternative anaplerotic substrates in utero.

Indexed as

Embryonic DevelopmentAlanine TransaminaseAnimalsBrainEmbryo, MammalianFemaleGenes, LethalHomozygoteLipid MetabolismLiverMetabolomicsMicePregnancyProprotein Convertase 1Pyruvic AcidAlanine TransaminasePcsk1 protein, mouseProprotein Convertase 1Pyruvic Acid

Identifiers

PMID27215380
PMCPMC4946427
OpenAlexW2396811662

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.