Regulation of mitochondrial biogenesis. Occurrence of non-functioning components of the mitochondrial respiratory chain in Saccharomyces cerevisiae grown in the presence of proteinase inhibitors: evidence for proteolytic control over assembly of the respiratory chain

Abstract

Yeast was grown in glucose- or galactose-containing media without or with proteinase inhibitors, phenylmethanesulphonyl fluoride and pepstatin. Culture growth was practically not affected by these compounds. Yeast growth on glucose in the presence of either phenylmethanesulphonyl fluoride or pepstatin entails accumulation of cytochromes c, c1, b and aa3 to a 25--30% excess above the control by the stationary phase, while cell respiration is unaffected. During growth on galactose the maximal cytochrome content (per unit weight of biomass) is reached in the mid-exponential phase and then decreases by 30--40% towards the stationary phase, while cell respiration remains constant. Addition of phenylmethanesulphonyl fluoride or pepstatin in the mid-exponential phase blocks the decrease in cytochrome levels and has no effect on cell respiration. Mitochondrial populations isolated from stationary-phase control and phenylmethanesulphonyl fluoride-grown cells glucose cultures display identical succinate oxidase and partial-respiratory-chain activities, despite the differences in cytochrome contents. However, the activities of individual respiratory complexes measured after maximal activation are nearly proportional to the amounts of corresponding components. The same situation holds true for mitochondrial populations from mid-exponential-phase, stationary-phase control and stationary-phase inhibitor-grown cells of galactose cultures. The findings suggest that the 'surplus' respiratory-chain components do not participate in electron flow because of the lack of interaction with adjacent carriers.

Glucose-induced inactivation of mitochondrial enzymes in the yeast Saccharomyces cerevisiae

“…Allan & Welman (1980) have reported that mitochondrial protein can be degraded by myocardial lysosomal enzymes in vitro. Also, Galkin et al (1980) have reported that proteinases regulate the yeast respiratory system. Our results are entirely in accord with these findings.…”

Quality control: from molecules to organelles

“…In support of this conjecture I can first mention that inhibition of vacuolar proteases in S. cerevisiae leads to intracellular accumulation of surplus cytochromes b , c 1 + c , and aa 3 [22]. There were grounds for believing that these cytochromes form potentially active enzymic complexes taking for some reasons no part in the mitochondrial respiration.…”

The role of protein degradation in mitochondrial function and biogenesis

“…This loss of cytochromes is inhibited by the protease inhibitors PMSF and pepstatin (Luzikov et al 1976). Administration of these inhibitors also increases the accumulation of cytochromes in glucose-grown cells (Galkin et al 1980). These changes in cytochrome content are not accompanied by changes in the activity of the respiratory chain complexes, indicating that the 'surplus' cytochromes accumulated during exponential growth are not functional (Galkin et al 1979a(Galkin et al , b, 1980.…”