Pharmacological modulators of autophagy activate a parallel noncanonical pathway driving unconventional LC3 lipidation.

ABSTRACT: The modulation of canonical macroautophagy/autophagy for therapeutic benefit is an emerging strategy of medical and pharmaceutical interest. Many drugs act to inhibit autophagic flux by targeting lysosome function, while others were developed to activate the pathway. Here, we report the surprising finding that many therapeutically relevant autophagy modulators with lysosomotropic and ionophore properties, classified as inhibitors of canonical autophagy, are also capable of activating a parallel noncanonical autophagy pathway that drives MAP1LC3/LC3 lipidation on endolysosomal membranes. Further, we provide the first evidence supporting drug-induced noncanonical autophagy in vivo using the local anesthetic lidocaine and human skin biopsies. In addition, we find that several published induce

SUBMITTER: Jacquin E 

PROVIDER: S-EPMC5446083 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature