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Pacing‐induced heart failure causes specific defects in the phosphorylation apparatus in skeletal muscle mitochondria
Author(s) -
Rosca Mariana G,
Vazquez Edwin J,
Kerner Janos,
Stanley William,
Recchia Fabio,
Hoppel Charles L
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.21.6.a945-c
Subject(s) - skeletal muscle , phosphorylation , oxidative phosphorylation , mitochondrion , heart failure , medicine , endocrinology , chemistry , adenine nucleotide , cardiac muscle , respiration , biochemistry , biology , anatomy , nucleotide , gene
Alterations in oxidation of substrates and the phosphorylation process in cardiac and skeletal muscle mitochondria may be a key mechanism in the pathogenesis of both myocardium and skeletal muscle dysfunction in heart failure (HF). Subsarcolemmal (SSM) and intefibrillar (IFM) mitochondria were isolated from gastrocnemius muscle of control dogs and dogs with pacing‐induced HF. HF was evident by an increase in end diastolic volume from 58±6 to 112±25 ml and a decrease in fractional shortening from 32±2% to 16±2% (Mean±SE, control vs HF, respectively). The significant decrease in oxidative phosphorylation in IFM was relieved in IFM upon raising the ADP concentration or uncoupling oxidation from the phosphorylation process. The activities of the individual ETC enzymes were in normal range in mitochondria isolated from HF dogs. These data demonstrate that the phosphorylation process rather than substrate oxidation is damaged with HF. A significant decrease in the activity of the ATP synthase was found specifically in skeletal muscle SSM. IFM have a significant decrease in the amount of the adenine nucleotide translocase 2 isoform. In conclusion, during moderate severity HF the different populations of skeletal muscle mitochondria develop specific defects localized in the phosphorylation apparatus.