Delivery of Cytosolic Components by Autophagic Adaptor Protein P62 Endows Autophagosomes with Unique Antimicrobial Properties

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2010 Mar 9

PMID 20206555

Citations 168

Authors

Marisa Ponpuak

Alexander S Davis

Esteban A Roberts

Monica A Delgado

Christina Dinkins

Zijiang Zhao

Herbert W Virgin 4th

George B Kyei

Terje Johansen

Isabelle Vergne

Vojo Deretic

Affiliations

Soon will be listed here.

Abstract

Autophagy allows cells to self-digest portions of their own cytoplasm for a multitude of physiological purposes, including innate and adaptive immunity functions. In one of its innate immunity manifestations, autophagy, is known to contribute to the killing of intracellular microbes, including Mycobacterium tuberculosis, although the molecular mechanisms have been unclear. Here, we delineated sequential steps of the autophagic pathway necessary to control intracellular M. tuberculosis and found that in addition to autophagy initiation and maturation, an accessory autophagy-targeting molecule p62 (A170 or SQSTM1) was required for mycobactericidal activity. The p62 adaptor protein delivered specific ribosomal and bulk ubiquitinated cytosolic proteins to autolysosomes where they were proteolytically converted into products capable of killing M. tuberculosis. Thus, p62 brings cytosolic proteins to autolysosomes where they are processed from innocuous precursors into neo-antimicrobial peptides, explaining in part the unique bactericidal properties of autophagic organelles.

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