Degradation of proteasomes by lysosomes in rat liver.
Proteasomes are high-molecular-mass multisubunit complexes which are believed, either by themselves or as a part of the 26S proteinase complex, to play a central role in extralysosomal pathways of intracellular protein breakdown. We have addressed the degradation of proteasomes in rat liver, investigating the possible role of lysosomes. Affinity-purified antibodies against rat liver proteasomes were used for immunoblot analysis of isolated lysosomes. Although proteasomes are not found in lysosomes from normally fed rats, they were found to accumulate in lysosomes of rats treated with leupeptin (an inhibitor of lysosomal proteases) and could also be detected in lysosomes isolated from livers of starved (24 h) rats. Proteinase-K treatment of these fractions, as well as immunogold procedures, show that a proportion of the proteasomes are inside lysosomes. Comparison of the amount of proteasomes found in lysosomes by immunoblotting with their experimentally determined half life (8.3 days) is consistent with an important role of these organelles in the degradation of rat liver proteasomes. Nevertheless, these data do not exclude the possibility that some nonlysosomal degradation of proteasome components also occurs. Since proteasomes were localized in autophagic vacuoles, it is likely that they are taken up mainly by nonselective autophagy. However, using an in vitro system, it was found that, under conditions of starvation, proteasomes may also be taken up into lysosomes and degraded via the heat-shock cognate protein of 73 kDa (hsc73)-mediated transport.
Cuervo
A M
AM
Instituto de Investigaciones Citológicas, Fundación Valenciana de Investigaciones Biomédicas, Spain.
Palmer
A
A
Rivett
A J
AJ
Knecht
E
E
D000818:Animals; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D005215:Fasting / Q000378:metabolism; D006207:Half-Life; D066298:In Vitro Techniques; D007976:Leupeptins / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D008247:Lysosomes / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D008297:Male; D016253:Microscopy, Immunoelectron; D009097:Multienzyme Complexes / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D051381:Rats; D017208:Rats, Wistar
D007976:Leupeptins; D009097:Multienzyme Complexes; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; C032854:leupeptin