DEGRADATION OF HMG-COA REDUCTASE-INDUCED MEMBRANES IN THE FISSION YEAST, SCHIZOSACCHAROMYCES-POMBE

Elevated levels of certain membrane proteins, including the sterol bio synthetic enzyme HMG-CoA reductase, induce proliferation of the endopl asmic reticulum. When the amounts of these proteins return to basal le vels, the proliferated membranes are degraded, but the molecular detai ls of this degradation remain unknown. We have examined the degradatio n of HMG-CoA reductase-induced membranes in the fission yeast, Schizos accharomyces pombe. In this yeast, increased levels of the Saccharomyc es cerevisine HMG-CoA reductase isozyme encoded by HMG1 induced severa l types of membranes, including karmellae, which formed a cap of stack ed membranes that partially surrounded the nucleus. When expression of HMC1 was repressed, the karmellae detached from the nucleus and forme d concentric, multilayered membrane whorls that were then degraded. Du ring the degradation process, CDCFDA-stained compartments distinct fro m preexisting vacuoles formed within the interior of the whorls. In ad dition to these compartments, particles that contained neutral lipids also formed within the whorl. As the thickness of the whorl decreased, the lipid particle became larger. When degradation was complete, only the lipid particle remained. Cycloheximide treatment did not prevent the formation of whorls. Thus, new protein synthesis was not needed fo r the initial stages of karmellae degradation. On the contrary, cycloh eximide promoted the detachment of karmellae to form whorls, suggestin g that a short lived protein may be involved in maintaining karmellae integrity. Taken together, these results demonstrate that karmellae me mbranes differentiated into self-degradative organelles. This process may be a common pathway by which ER membranes are turned over in cells .