Chronic stimulation of rat skeletal muscle induces coordinate increases in mitochondrial and nuclear mRNAs of cytochrome‐c‐oxidase subunits

Abstract

Fast‐twitch tibialis anterior muscle of the rat was subjected to chronic low‐frequency (10 Hz, 10 h daily) nerve stimulation in order to investigate the time course of changes in cytochrome‐c‐oxidase activity, as well as in tissue levels of specific mitochondrially and nuclear‐encoded, cytochrome‐c‐oxidase‐subunit mRNAs. Chronic stimulation induced a progressive increase in cytochrome‐c‐oxidase activity which was threefold elevated after 35 days. A similar increase was recorded for citrate‐synthase activity. Glyceraldehyde‐3‐phosphate dehydrogenase, which was studied as a glycolytic reference enzyme, moderately decreased, as did the tissue level of its corresponding mRNA. There was a parallel increase in the tissue levels of the two cytochrome‐c‐oxidase‐subunit mRNAs over the entire stimulation time course. The extent of increase (stimulated/control) was 2.4 ± 0.3 and 1.8 ± 0.2 (means ± SEM) for the mitochondrial and nuclear subunit mRNAs, respectively. This parallel increase suggested a coordinate regulation of the two subunits. The increase in cytochrome‐c‐oxidase activity initially corresponded to the changes at the mRNA level. However, with longer stimulation times (beyond 14 days), the increase in cytochrome‐c‐oxidase activity clearly exceeded that of the two mRNAs. This divergence was progressive and was interpreted to indicate that the increase in cytochrome‐c‐oxidase content was brought about not only by changes in the levels of the specific mRNAs, but also by alterations at the level of translation. Copyright © 1989, Wiley Blackwell. All rights reserved