Delivery of Cytosolic Components by Autophagic Adaptor Protein p62 Endows Autophagosomes with Unique Antimicrobial Properties

Marisa Ponpuak, Alexander S. Davis, Esteban A. Roberts, Monica A. Delgado, Christina Dinkins, Zijiang Zhao, Herbert W. Virgin, George B. Kyei, Terje Johansen, Isabelle Vergne, Vojo Deretic

Research output: Contribution to journalArticle

209 Scopus citations

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.

Original languageEnglish
Pages (from-to)329-341
Number of pages13
JournalImmunity
Volume32
Issue number3
DOIs
StatePublished - Mar 1 2010

Keywords

  • MOLIMMUNO

Fingerprint Dive into the research topics of 'Delivery of Cytosolic Components by Autophagic Adaptor Protein p62 Endows Autophagosomes with Unique Antimicrobial Properties'. Together they form a unique fingerprint.

  • Cite this

    Ponpuak, M., Davis, A. S., Roberts, E. A., Delgado, M. A., Dinkins, C., Zhao, Z., Virgin, H. W., Kyei, G. B., Johansen, T., Vergne, I., & Deretic, V. (2010). Delivery of Cytosolic Components by Autophagic Adaptor Protein p62 Endows Autophagosomes with Unique Antimicrobial Properties. Immunity, 32(3), 329-341. https://doi.org/10.1016/j.immuni.2010.02.009