The Serine Protease from Rat Liver and Hepatoma 8999 Location and Role in Mitochondrial Protein Degradation1

1. Hepatoma 8999 showed extremely high activity of serine protease, but similar activities of other lysosomal proteases to those of normal rat liver. 2. Serine protease from rat liver formed a single immunoprecipitation band against antiserum to purified protease from hepatoma 8999. 3. The serine proteases in rat liver and hepatoma 8999 were restricted to the inner membranes of the mitochondrial fraction. 4. Polyacrylamide gel electrophoresis with sodium dodecylsulfate showed that hepatoma 8999 mitochondria contained less of the slowest moving protein compo-nent than rat liver mitochondrial protein. This component was found to be the best substrate for mitochondrial serine protease in both liver and hepatoma 8999. 5. The role of serine pro-tease in mitochondrial protein degradation is discussed on the basis of these results. It has been reported that there are protease systems outside the protective membranes of lysosomes of rat liver, in sub-cellular compartments such as the endoplasmic reticulum (1), peroxisomes (2), the nuclei {3-5), and mitochondria (6-9). The roles of these proteases in selective degradation of proteins in different cell compartments are still unknown. The early studies of Fletcher and Sanadi (70) indicated that the mitochondria turn over as an entity at the same rate, but many other reports suggest that individual mitochondrial com-ponents turn over at different rates (11-13); for example, 5-aminolevulinate synthetase (14) an