Every time a bout of exercise is performed, a change in gene expression occurs

within the contracting muscle. Over the course of many repeated bouts of

exercise (i.e. training), the cumulative effects of these alterations lead to a

change in muscle phenotype. One of the most prominent of these adaptations

is an increase in mitochondrial content, which confers a greater resistance to

muscle fatigue. This essay reviews current knowledge on the regulation of

exercise-induced mitochondrial biogenesis at the molecular level. The major

steps involved include, (i) transcriptional regulation of nuclear-encoded genes

encoding mitochondrial proteins by the coactivator peroxisome-proliferatoractivated

receptor coactivator-1, (ii) control of mitochondrial DNA gene

1To whom correspondence should be addressed (email dhood@yorku.ca).

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14 Essays in Biochemistry volume 42 2006

expression by the transcription factor Tfam, (iii) mitochondrial fi ssion and

fusion mechanisms, and (iv) import of nuclear-derived gene products into

the mitochondrion via the protein import machinery. It is now known that

exercise can modify the rates of several of these steps, leading to mitochondrial

biogenesis. An understanding of how exercise can produce this effect could

help us decide whether exercise is beneficial for patients suffering from

mitochondrial disorders, as well as a variety of metabolic diseases.