Premium
Role of uncoupling protein‐3 in fatty acid oxidation in skeletal muscle mitochondria
Author(s) -
Seifert Erin Leah,
Bezaire Veronic,
Harper MaryEllen
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a667
Subject(s) - ucp3 , mitochondrial matrix , uncoupling protein , carnitine , mitochondrion , chemistry , beta oxidation , biochemistry , fatty acid , skeletal muscle , palmitoylcarnitine , biology , cytosol , endocrinology , enzyme , brown adipose tissue , adipose tissue
BACKGROUND : Himms‐Hagen and Harper (Exp Biol Med 2001) hypothesized that uncoupling protein‐3 (UCP3) provides an overflow pathway for fatty acids (FA) in conditions of excess mitochondrial FA supply. Thus when FA flux to mitochondria is greatly elevated, long chain FA‐CoA accumulates in the matrix, sequestering the limited matrix CoA pool and preventing oxidation of partially metabolized FA. UCP3 would act with a mitochondrial thioesterase to liberate CoA and export FA anions. A functional implication of matrix FA anion export by UCP3 is increased FA oxidation (FAO) in conditions of high FA flux. AIM : Directly test the hypothesis that UCP3 facilitates FAO by exporting FA. APPROACH : FAO rates (14CO2 production) were measured in skeletal muscle mitochondria of wild‐type (WT) and UCP3−/− (KO) mice under several conditions: a range of 14C‐palmitate (PA) or 14C‐palmitoylcarnitine (PC) concentrations to simulate low and high FA supply; presence/absence of CoA during PC oxidation to interfere with reactivation of potential exported FA; addition/omission of carnitine during PC oxidation to modify matrix acyl‐CoA/CoA. Generated and exported PA: measured by thin‐layer chromatography. Data analysis: unpaired t‐test or 2‐way ANOVA (n = 4–6). RESULTS: Generated and exported PA were detected, with no difference between WT and KO mitochondria. PA and PC rates were similar between WT and KO, at low and high FA flux, and in the presence/absence of carnitine. Addition of 0.05 μM CoA similarly increased CO2 production in both genotypes. CONCLUSION: Our observations do not support an obligatory role for UCP3 in facilitating FAO or in export of PA in isolated skeletal muscle mitochondria, even when FA supply is greatly elevated. Funding: CIHR