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Funded Studies

Role of Parkin in Innate Immunity

The protein Parkin contributes to the elimination of damaged mitochondria by a process called mitophagy. Prior research has shown that silencing Parkin gene affects innate immunity, the first line of defense against invading viruses. This project will characterize the mechanisms by which Parkin modulates host immune response. One of the key players in innate immunity is a mitochondrial antiviral signaling protein (MAVS). MAVS interacts with Parkin, and researchers hypothesize that this association may lead to the degradation of MAVS, via Parkin’s E3 ubiquitin ligase (degradation) activity. If MAVS is degraded, subsequent steps of the pathway to counter viral attack and spread are compromised. 

Project Description:
Using myriad experimental methods, researchers will first purify and characterize the MAVS-Parkin complex on mitochondria. Parkin mutants will be used to confirm the functional role of Parkin. Next, researchers will monitor MAVS degradation and monitor inhibition of antiviral interferon (IFN) synthesis. IFN is an antiviral protein, which limits viral spread. IFN also induces a whole host of genes to provide a strong line of defense against invading microbes. This work will characterize IFN and IFN-stimulated gene expression after inducing degradation of MAVS by Parkin. 

Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Parkin mutations that spontaneously arise in nature may disable innate immunity pathways, and thus patients carrying these mutations may be vulnerable to viral/bacterial infections. While more research will be needed to characterize the steps of innate immunity affected by Parkin’s modulatory property, recognition of Parkin and MAVS association with mitochondria can be an initial step in the diagnosis.

Anticipated Outcome:
Researchers anticipate that this project will reveal a novel role of the Parkin gene in inducing innate immunity and that if the Parkin gene is changed (mutated) in people with Parkinson’s disease, its functions will be changed, as well, including its ability to protect from germs and pathogens. This study will open up new avenues of diagnosis and treatment strategies directed toward restoring Parkin’s normal function and disrupting Parkin-MAVS association and subsequent inactivation of downstream signaling.


  • Aleem Siddiqui, PhD

    La Jolla, CA United States

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