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Cardiac MuRF1 expression alters mitochondrial oxidative phosphorylation function in vivo
Author(s) -
Willis Monte S,
Rodriguez Jessica E,
Zungu Makhosazane
Publication year - 2010
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.24.1_supplement.lb408
Subject(s) - oxidative phosphorylation , mitochondrion , oligomycin , medicine , chemistry , biochemistry , biology , endocrinology , enzyme , atpase
Muscle ring finger 1 (MuRF1) is a cardiac‐specific ubiquitin ligase regulating cardiac atrophy and fatty acid metabolism. Here, we examined the effects of cardiac‐specific over expression (MuRF1 Tg+) and ablation (MuRF1 −/−) of MuRF1 on mitochondrial bioenergetics in the heart. Cardiac mitochondrial respiration parameters were measured using a Clark‐type oxygen electrode using a combination of malate (M), palmitoyl‐L‐carnitine (CP), pyruvate (P) and succinate (S) as oxidative substrates. The oligomycin‐insensitive basal proton leak was augmented in the MuRF1 Tg+ cardiac mitochondria by 40 ± 2.4% (n=5; p<0.05 vs. wild‐type control) when M+P were used as oxidative substrates. The respiratory control index (RCI), a marker of mitochondrial viability, was increased in the MuRF1 −/− mice by 48 ± 4.5% (n=5; p<0.05 vs. wild type control) when succinate was employed as an oxidative substrate. No significant changes were observed in the other mitochondrial parameters measured. Our data demonstrate that increased cardiac MuRF1 expression results in impaired mitochondrial oxidative phosphorylation as a result of increased basal proton leak, which may explain the increased susceptibility to heart failure we have identified in MuRF1 Tg+ hearts.