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Mechanisms of Mitochondrial Damage Control by PINK1 and Parkin

Study Rationale:
Mitochondria are tiny power-generating stations within all cells, including neurons. They are vital energy producers, but when things go wrong, they can spew toxic materials and sicken or kill neurons. The clean up crew for mitochondria gone wrong is called "mitophagy" (as in "eating mitochondria") and is directed by two proteins called PINK1 and parkin. Studies of Parkinson's disease have taught us that PINK1, parkin and mitophagy are very important in preventing disease.

The purpose of this project is to figure out how PINK1, parkin and mitophagy work together to prevent disease. Once we know how they work together, we hope to figure out how to make them work faster and better, so that we can prevent Parkinson's disease from ever starting.

Study Design:
We think of PINK1, parkin and the proteins of mitophagy as nanomachines. We call our type of research "mechanistic" because it seeks to understand how these machines work. We rely heavily on the most powerful light and electron microscopes available, and we also use genome engineering of stem cells to make versions of neurons that are easier to study.

Impact on Diagnosis/Treatment of Parkinson’s Disease:
Our dream is to understand PINK1, parkin and mitophagy so well that we can build a computerized description of the pathway that will be able to predict which drugs and treatments will help the mitochondrial clean up crew enough to prevent or cure disease.

Next Steps for Development:
Once we have figured out which of the gears and switches of the machines are the best ones to tweak to improve performance, we can use the images taken by electron microscopy to help design drugs to prevent or cure disease.


  • James Herschel Hurley, PhD

    Berkeley, CA United States

  • Erika L.F. Holzbaur, PhD

    Philadelphia, PA United States

  • Michael Lazarou, PhD

    Melbourne VIC Australia

  • Sascha Martens, Dr rer nat

    Vienna Austria

  • Eunyong Park, PhD

    Berkeley, CA United States

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