The ubiquitin ligase parkin mediates resistance to intracellular pathogens

Paolo S. Manzanillo, Janelle S. Ayres, Robert O. Watson, Angela C. Collins, Gianne Souza, Chris S. Rae, David S. Schneider, Ken Nakamura, Michael U. Shiloh, Jeffery S. Cox

Research output: Contribution to journalArticlepeer-review

423 Scopus citations


Ubiquitin-mediated targeting of intracellular bacteria to the autophagy pathway is a key innate defence mechanism against invading microbes, including the important human pathogen Mycobacterium tuberculosis. However, the ubiquitin ligases responsible for catalysing ubiquitin chains that surround intracellular bacteria are poorly understood. The parkin protein 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 enterica serovar Typhi, but the function of parkin in immunity has remained unexplored. Here we show that parkin has a role in ubiquitin-mediated autophagy of M. tuberculosis. Both parkin-deficient mice and flies are sensitive to various intracellular bacterial infections, indicating parkin has a conserved role in metazoan innate defence. Moreover, our work reveals an unexpected functional link between mitophagy and infectious disease.

Original languageEnglish (US)
Pages (from-to)512-516
Number of pages5
Issue number7468
StatePublished - 2013

ASJC Scopus subject areas

  • General


Dive into the research topics of 'The ubiquitin ligase parkin mediates resistance to intracellular pathogens'. Together they form a unique fingerprint.

Cite this