PARKIN ubiquitin ligase mediates resistance to intracellular pathogens

Ubiquitin-mediated targeting of intracellular bacteria to the autophagy pathway is a key innate defense mechanism against invading microbes, including the important human pathogen Mycobacterium tuberculosis. However, the ubiquitin ligases responsible for catalyzing ubiquitin chains that surround int...

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Main Authors:	Manzanillo, Paolo S., Ayres, Janelle S., Watson, Robert O., Collins, Angela C., Souza, Gianne, Rae, Chris S., Schneider, David S., Nakamura, Ken, Shiloh, Michael U., Cox, Jeffery S.
Format:	Online
Language:	English
Published:	2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3886920/

id	pubmed-3886920
recordtype	oai_dc
spelling	pubmed-38869202014-03-26 PARKIN ubiquitin ligase mediates resistance to intracellular pathogens Manzanillo, Paolo S. Ayres, Janelle S. Watson, Robert O. Collins, Angela C. Souza, Gianne Rae, Chris S. Schneider, David S. Nakamura, Ken Shiloh, Michael U. Cox, Jeffery S. Article Ubiquitin-mediated targeting of intracellular bacteria to the autophagy pathway is a key innate defense mechanism against invading microbes, including the important human pathogen Mycobacterium tuberculosis. However, the ubiquitin ligases responsible for catalyzing ubiquitin chains that surround intracellular bacteria are poorly understood. PARKIN is a ubiquitin ligase with a well-established role in mitophagy, and mutations in the PARKIN gene (Park2) lead to increased susceptibility to Parkinson’s disease. Surprisingly, genetic polymorphisms in the Park2 regulatory region are also associated with increased susceptibility to intracellular bacterial pathogens in humans, including Mycobacterium leprae and Salmonella typhi, but the function of PARKIN in immunity remains unexplored. Here we show that PARKIN plays a role in ubiquitin-mediated autophagy of M. tuberculosis. Both PARKIN-deficient mice and flies are sensitive to various intracellular bacterial infections, suggesting PARKIN plays a conserved role in metazoan innate defense. Moreover, our work reveals an unexpected functional link between mitophagy and infectious disease. 2013-09-04 2013-09-26 /pmc/articles/PMC3886920/ /pubmed/24005326 http://dx.doi.org/10.1038/nature12566 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Manzanillo, Paolo S. Ayres, Janelle S. Watson, Robert O. Collins, Angela C. Souza, Gianne Rae, Chris S. Schneider, David S. Nakamura, Ken Shiloh, Michael U. Cox, Jeffery S.
spellingShingle	Manzanillo, Paolo S. Ayres, Janelle S. Watson, Robert O. Collins, Angela C. Souza, Gianne Rae, Chris S. Schneider, David S. Nakamura, Ken Shiloh, Michael U. Cox, Jeffery S. PARKIN ubiquitin ligase mediates resistance to intracellular pathogens
author_facet	Manzanillo, Paolo S. Ayres, Janelle S. Watson, Robert O. Collins, Angela C. Souza, Gianne Rae, Chris S. Schneider, David S. Nakamura, Ken Shiloh, Michael U. Cox, Jeffery S.
author_sort	Manzanillo, Paolo S.
title	PARKIN ubiquitin ligase mediates resistance to intracellular pathogens
title_short	PARKIN ubiquitin ligase mediates resistance to intracellular pathogens
title_full	PARKIN ubiquitin ligase mediates resistance to intracellular pathogens
title_fullStr	PARKIN ubiquitin ligase mediates resistance to intracellular pathogens
title_full_unstemmed	PARKIN ubiquitin ligase mediates resistance to intracellular pathogens
title_sort	parkin ubiquitin ligase mediates resistance to intracellular pathogens
description	Ubiquitin-mediated targeting of intracellular bacteria to the autophagy pathway is a key innate defense mechanism against invading microbes, including the important human pathogen Mycobacterium tuberculosis. However, the ubiquitin ligases responsible for catalyzing ubiquitin chains that surround intracellular bacteria are poorly understood. PARKIN is a ubiquitin ligase with a well-established role in mitophagy, and mutations in the PARKIN gene (Park2) lead to increased susceptibility to Parkinson’s disease. Surprisingly, genetic polymorphisms in the Park2 regulatory region are also associated with increased susceptibility to intracellular bacterial pathogens in humans, including Mycobacterium leprae and Salmonella typhi, but the function of PARKIN in immunity remains unexplored. Here we show that PARKIN plays a role in ubiquitin-mediated autophagy of M. tuberculosis. Both PARKIN-deficient mice and flies are sensitive to various intracellular bacterial infections, suggesting PARKIN plays a conserved role in metazoan innate defense. Moreover, our work reveals an unexpected functional link between mitophagy and infectious disease.
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3886920/
_version_	1612046181828919296

PARKIN ubiquitin ligase mediates resistance to intracellular pathogens

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