3-Methyladenine: Specific Inhibitor of Autophagic/lysosomal Protein Degradation in Isolated Rat Hepatocytes

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1982 Mar 1

PMID 6952238

Citations 591

Authors

P O Seglen

P B Gordon

Affiliations

Soon will be listed here.

Abstract

3-Methyladenine (5 mM) inhibits endogenous protein degradation in isolated rat hepatocytes by about 60%, while having no adverse effect on the degradation of an exogenous protein (asialofetuin), on protein synthesis, or on intracellular ATP levels. 3-Methyladenine appears to act specifically upon the autophagic/lysosomal pathway of degradation, as judged from its lack of effect in the presence of amino acids or a lysosomotropic amine (propylamine). The effect of the purine is not mediated by amino acids because the inhibition of protein degradation is accompanied by a significant depression of intracellular amino acid levels. The ability of 3-methyladenine to suppress the formation of electron microscopically visible autophagosomes suggests that it may be regarded as a specific inhibitor of autophagy.

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