Plasticity in Skeletal, Cardiac, and Smooth Muscle: Selected Contribution: Effects of contractile activity on mitochondrial transcription factor A expression in skeletal muscle
1 Kinesiology and Health Science, Faculty of Pure and Applied Science, York University, Toronto, Ontario, Canada M3J 1P3; and 2 Department of Chemistry, National Industrial Research Institute of Nagoya, Nagoya 462, Japan Mitochondrial transcription factor A (Tfam) is a nuclear-encoded gene product...
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Published in | Journal of applied physiology (1985) Vol. 90; no. 1; pp. 389 - 396 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
Bethesda, MD
Am Physiological Soc
01.01.2001
American Physiological Society |
Subjects | |
Online Access | Get full text |
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Summary: | 1 Kinesiology and Health Science, Faculty of Pure and
Applied Science, York University, Toronto, Ontario,
Canada M3J 1P3; and 2 Department of Chemistry,
National Industrial Research Institute of Nagoya, Nagoya 462, Japan
Mitochondrial
transcription factor A (Tfam) is a nuclear-encoded gene product that is
imported into mitochondria and is required for the transcription of
mitochondrial DNA (mtDNA). We hypothesized that conditions known to
produce mitochondrial biogenesis in skeletal muscle would be preceded
by an increase in Tfam expression. Therefore, rat muscle was stimulated
(10 Hz, 3 h/day). Tfam mRNA levels were significantly elevated (by
55%) at 4 days and returned to control levels at 14 days. Tfam import
into intermyofibrillar (IMF) mitochondria was increased by 52 and 61%
( P < 0.05) at 5 and 7 days, respectively. This corresponded
to an increase in the level of import machinery components.
Immunoblotting data indicated that IMF Tfam protein content was
increased by 63% ( P < 0.05) at 7 days of stimulation. This was associated with a 49% ( P < 0.05) increase in
complex formation at the mtDNA promoter and a 65% ( P < 0.05) increase in the levels of a mitochondrial transcript,
cytochrome- c oxidase (COX) subunit III. Similarly, COX
enzyme activity was elevated by 71% ( P < 0.05) after
7 days of contractile activity. These results indicate that early
events in mitochondrial biogenesis include increases in Tfam mRNA,
followed by accelerations in mitochondrial import and increased
Tfam content, which correspond with increased binding to the
mtDNA promoter region. This was accompanied by increased mitochondrial
transcript levels and elevated COX activity. These data support the
role of Tfam as a regulatory protein involved in contractile
activity-induced mitochondrial biogenesis.
mitochondrial biogenesis; mitochondrial protein import |
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ISSN: | 8750-7587 1522-1601 |