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Mitochondrial function and protein expression profile in skeletal muscle from PGC‐1α null mice
Author(s) -
Adhihetty Peter J,
Pilegaard Henriette,
Leick Lotte,
Florit Sergi,
Comes Gemma,
Hidalgo Juan,
Hood David A
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.a938-a
Subject(s) - mitochondrial biogenesis , tfam , mitochondrion , biology , skeletal muscle , fis1 , organelle biogenesis , microbiology and biotechnology , medicine , mitochondrial dna , endocrinology , biogenesis , biochemistry , mitochondrial fusion , gene
PPAR‐gamma coactivator‐1α (PGC‐1α) is an important regulator of mitochondrial biogenesis. However, its effect on mitochondrial function, key regulatory proteins involved in organelle synthesis and apoptosis are not resolved in skeletal muscle, particularly in intermyofibrillar (IMF) and subsarcolemmal (SS) subfractions. Thus, we examined respiration, ROS production and protein expression in mitochondria from PGC‐1α null animals. SS and IMF mitochondrial yields in muscle from PGC‐1α null animals was 36% and 27% (p<0.05) lower, than in wild‐type animals. Parallel decrements of 22% and 36% (p<0.05) existed in the mitochondrial markers, COX activity and cytochrome c. Despite these differences, the mtDNA transcription factor Tfam, and mitochondrial fission protein Fis1, were similar in null and wild‐type animals. However, the import protein mtHSP70 was 30% lower in muscle from PGC‐1α null animals. The Bax:Bcl‐2 ratio, an apoptotic indicator, was unaltered but both proteins were 35% greater in muscle from PGC‐1α null animals. SS mitochondria from PGC‐1α null animals displayed 35% and 20% lower respiration rates and ROS production, respectively, while IMF mitochondria exhibited no differences compared to wild‐type. Thus, the absence of PGC‐1α does not completely reduce mitochondrial content and must evoke compensatory mechanisms to prevent the entire loss of mitochondrial function in muscle.