How proteins get into microbodies (peroxisomes, glyoxysomes, glycosomes).

All microbody proteins studies, including one microbody membrane protein, are made on free polysomes and imported post-translationally. This holds for animal tissues, plants, and fungi. The majority of microbody protein sub-units are synthesized in a form not detectably different from mature sub-units. In five cases a larger precursor protein has been found. The position of the extra piece in this precursor is not known. In two of the five cases, processing of the precursor is not coupled to import; in the other three this remains to be determined. It is not even known whether information in the prepiece contributes to topogenesis, or serves other purposes. Microbody preparations from Neurospora, plant tissue and rat liver can take up some newly synthesized microbody proteins in vitro. In most cases uptake is inefficient. No special requirements for uptake have been established and whether a receptor is involved is not yet known. Several examples have been reported of peroxisomal enzymes with a counterpart in another cell compartment. With the exception of catalase, no direct evidence is available in any of these cases for two isoenzymes specified by the same gene. In the Zellweger syndrome, a lethal hereditary disease of man, characterized by a lack of peroxisomes, the levels of several enzymes of lipid metabolism are strongly decreased. In contrast, D-amino-acid oxidase, L-alpha-hydroxyacid oxidase and catalase levels are normal. The catalase resides in the cytosol. Since there is no separate gene for cytosolic catalase, the normal catalase levels in Zellweger cells show that some peroxisomal enzymes can mature and survive stably in the cytosol. It is possible that maturation of the peroxisomal enzyme in the cytoplasm can account for the finding of cytosolic catalase in some normal mammalian cells. The glycosomes of trypanosomes are microbodies that contain a glycolytic system. Comparison of the glycosomal phosphoglycerate kinase with its cytosolic counterpart has shown that these isoenzymes are 93% homologous in amino-acid sequence, but less than 50% homologous to the corresponding enzymes of yeast and mammals. This implies that few alterations are required to direct a protein into microbodies. This interpretation is supported by the evidence for homology between some microbody and mitochondrial isoenzymes in other organisms mentioned under point 4. The major changes of the glycosomal phosphoglycerate kinase relative to the cytosolic enzyme are a large increase in positive charge and a C-terminal extension of 20 amino acids.(ABSTRACT TRUNCATED AT 400 WORDS)