3-Methyladenine: specific inhibitor of autophagic/lysosomal protein degradation in isolated rat hepatocytes

PO Seglen, PB Gordon - Proceedings of the National …, 1982 - National Acad Sciences
PO Seglen, PB Gordon
Proceedings of the National Academy of Sciences, 1982National Acad Sciences
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 …
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.
National Acad Sciences