UCP2-dependent proton leak in isolated mammalian mitochondria

Brian D Fink; Young-Sun Hong; Mary M Mathahs; Thomas D Scholz; Joseph S Dillon; William I Sivitz

doi:10.1074/jbc.M107955200

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UCP2-dependent proton leak in isolated mammalian mitochondria

Journal article

Open access

Peer reviewed

UCP2-dependent proton leak in isolated mammalian mitochondria

Brian D Fink, Young-Sun Hong, Mary M Mathahs, Thomas D Scholz, Joseph S Dillon and William I Sivitz

The Journal of biological chemistry, Vol.277(6), pp.3918-3925

02/08/2002

DOI: 10.1074/jbc.M107955200

PMID: 11723122

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Abstract

A role for uncoupling protein (UCP) homologues in mediating the proton leak in mammalian mitochondria is controversial. We subjected insulinoma (INS-1) cells to adenoviral expression of UCP2 or UCP1 and assessed the proton leak as the kinetic relationship between oxygen use and the inner mitochondrial membrane potential. Cells were infected with different amounts of rat UCP2, and, in other experiments, with either UCP2 or UCP1. The relative molar expression of these subtypes was quantified through comparison with histidine-tagged UCP1 or UCP2 proteins engineered by expression in Escherichia coli. Adenoviral infection with UCP2, compared with beta-galactosidase, resulted in a dose-dependent shift in kinetics indicating increased H(+) flux at any given membrane potential. UCP1 also enhanced H(+) flux, but, on a relative molar basis, the overexpression of the endogenous protein, UCP2, was more potent than UCP1. These results were not due to nonspecific overexpression of mitochondrial protein since UCP1 activity was inhibited by GDP and because overexpression of another membrane carrier protein, the oxoglutarate malate carrier had no effect. UCP2-mediated H(+) conduction was not GDP sensitive. These data suggest that the UCP homologue, UCP2, mediates the proton leak in mitochondria of a mammalian cell wherein UCP2 is the native subtype.

Carrier Proteins - physiology

Protons

Cell Line

Proteins - physiology

Ion Channels

Carrier Proteins - antagonists & inhibitors

Rats

Mitochondria - metabolism

Mitochondria - drug effects

DNA Primers

Mitochondrial Proteins

Proteins - genetics

Animals

Membrane Potentials

Membrane Proteins - antagonists & inhibitors

Escherichia coli - genetics

Membrane Proteins - physiology

Base Sequence

Membrane Transport Proteins

Ion Transport

Uncoupling Protein 2

Uncoupling Protein 1

beta-Galactosidase - genetics

Guanosine Diphosphate - pharmacology

Details

Title: Subtitle: UCP2-dependent proton leak in isolated mammalian mitochondria
Creators: Brian D Fink - Department of Internal Medicine, Divisions of Endocrinology and Metabolism, Iowa City Veterans Affairs Medical Center and the University of Iowa, Iowa City, Iowa 55246, USA
Young-Sun Hong
Mary M Mathahs
Thomas D Scholz
Joseph S Dillon
William I Sivitz
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.277(6), pp.3918-3925
DOI: 10.1074/jbc.M107955200
PMID: 11723122
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Grant note: R01 AG018928 / NIA NIH HHS HD29569 / NICHD NIH HHS DK25295 / NIDDK NIH HHS
Language: English
Date published: 02/08/2002
Academic Unit: Cardiology; Stead Family Department of Pediatrics; Fraternal Order of Eagles Diabetes Research Center; Child and Community Health; Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984093343802771

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