Human Disease Model Report: mitochondrial pyruvate carrier deficiency

General Information

Name

mitochondrial pyruvate carrier deficiency

FlyBase ID

FBhh0000724

Disease Ontology Term

mitochondrial pyruvate carrier deficiency

Parent Disease

OMIM

MITOCHONDRIAL PYRUVATE CARRIER DEFICIENCY; MPYCD

Overview

This report describes mitochondrial pyruvate carrier deficiency (MPYCD); MPYCD exhibits autosomal recessive inheritance. The human gene implicated in this disease is MPC1 (previously designated BRP44L), which encodes a protein the is part of the MPC1/MPC2 heterodimer that is responsible for transporting pyruvate into mitochondria. There is a single orthologous gene in Drosophila, Dmel\Mpc1, for which amorphic alleles resulting from imprecise excision of an insertion, RNAi targeting constructs, and alleles caused by insertional mutagenesis have been generated.

The human MPC1 gene has not been introduced into flies.

Animals homozygous for amorphic mutations of Dmel\Mpc1 are sensitive to a carbohydrate-only diet, dying shortly after transfer to a sucrose medium. They exhibit expected signs of impaired pyruvate metabolism, with an accumulation of upstream metabolites and a depletion of tricarboxylic acid cycle intermediates.

Mpc1 also plays a role in regulation of mitochondrial pyruvate metabolism in stem cell maintenance and differentiation. Targeted knockdown of Mpc1 in intestinal stem cells via RNAi increases proliferation; Mpc1 overexpression suppresses stem cell proliferation.

[updated May 2021 by FlyBase; FBrf0222196]

Disease Summary Information

Disease Summary: mitochondrial pyruvate carrier deficiency

OMIM report

[MITOCHONDRIAL PYRUVATE CARRIER DEFICIENCY; MPYCD](https://omim.org/entry/614741)

Human gene(s) implicated

[MITOCHONDRIAL PYRUVATE CARRIER 1; MPC1](https://omim.org/entry/614738)

Symptoms and phenotype

Mitochondrial pyruvate carrier deficiency is characterized by delayed psychomotor development and lactic acidosis with a normal lactate/pyruvate ratio resulting from impaired mitochondrial pyruvate oxidation (summary by Bricker et al., 2012; FBrf0218824) [from MIM:614741; 2018.02.12]

(OMIM, 2013-)

Genetics

Mitochondrial pyruvate carrier deficiency (MPYCD) is caused by homozygous mutation in the MPC1 gene (gene also designated BRP44L). [from MIM:614741; 2018.02.12]

(OMIM, 2013-)

Cellular phenotype and pathology

Molecular information

In mitochondria, pyruvate is converted into acetyl-coenzyme A (acetyl-CoA) by the pyruvate dehydrogenase complex. Uptake of pyruvate into mitochondria is mediated by a heterocomplex formed between MPC1 (BRP44L) and MPC2 (BRP44) (Herzig et al., 2012; pubmed:22628554).

(OMIM, 2013-)

External links

Gene2Function (human gene): MPC1
Gene Cards: MPC1
MedlinePlus (gene): MPC1
MARRVEL (human gene): MPC1
NCBI MedGen: Mitochondrial pyruvate carrier deficiency (MPYCD)
NCBI (Entrez) gene: MPC1; mitochondrial pyruvate carrier 1

Disease synonyms

MPYCD

Related Diseases

Related human health report(s)

cancer, intestinal stem cell models

Ortholog Information

Human gene(s) in FlyBase

Human gene (HGNC)

Symbol / Name

MPC1; mitochondrial pyruvate carrier 1

D. melanogaster ortholog (based on DIOPT)

Dmel\Mpc1

(DIOPT, 2013-)

Comments on ortholog(s)

One to one: 1 human to 1 Drosophila

Other mammalian ortholog(s) used

D. melanogaster Gene Information (1)

Dmel\Mpc1

Gene Snapshot

Mitochondrial pyruvate carrier 1 (Mpc1) encodes an obligate subunit of the mitochondrial pyruvate carrier, which transports pyruvate across the mitochondrial inner membrane. [Date last reviewed: 2019-03-14]

Molecular function (GO)