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Does Mitochondrial Uncoupling Generate More Mitochondria in Muscle?
Author(s) -
Conley Kevin E.,
Jubrias Sharon A,
Shankland Eric,
Amara Catherine E,
Marcinek David J
Publication year - 2009
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.23.1_supplement.600.30
Subject(s) - oxidative phosphorylation , mitochondrion , mitochondrial biogenesis , medicine , atp synthase , chemistry , biology , endocrinology , microbiology and biotechnology , biochemistry , enzyme
Uncoupling of oxidative phosphorylation (low ATP/O2 or P/O) has been proposed to trigger the signaling pathway governing mitochondrial biogenesis. Here we test whether uncoupling accounts for variation in mitochondrial oxidative capacity (O2max) among muscles. Mitochondrial P/O and O2max were determined in a range of human muscles in vivo using a combination of magnetic resonance and optical spectroscopic tools. O2max was directly proportional to mitochondrial content in the four human muscles studied. These muscles ranged from well‐coupled (P/O =2.7+0.1, n=10, first dorsal interosseous of the hand, FDI) to 50% uncoupled (P/O =1.5+0.3, n=5, soleus) and showed a corresponding 2‐fold range of O2max. Similarly, O2max varied with the degree of uncoupling in hand muscle (FDI) between healthy adults and those uncoupled by pathology. Thus a proportionality is found between the extent of uncoupling and O2max among muscles and for a single muscle differing in coupling due to disease. These data support the hypothesis that uncoupling activates the signaling pathway governing mitochondrial biogenesis and may play an important role in the variation in mitochondrial content among muscles and with disease.