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Funded Studies

Parkin as a Protection Against Mitochondrial Stress

Promising Outcomes of Original Grant:
Parkin is one of the key proteins linked to Parkinson's disease (PD). Previously, we examined if enhanced function of parkin changes the composition and renewal of proteins in mitochondria, the powerhouses of the cell. We conducted those studies using pre-clinical models with altered parkin: lacking this protein, producing this protein in excess or producing an activated form of the protein. We found that mitochondria located in the striatum (a brain region affected in PD) did not work properly in the absence of parkin, but excess or activation of parkin did not change mitochondrial function. Furthermore, parkin shortage, excess and activation changed how quickly proteins in striatal mitochondria were renewed. We determined the role parkin plays in regulating the protein composition of mitochondria in the striatum and how changes in mitochondrial proteins affect energy the mitochondria supply.

Objectives for Supplemental Investigation:
Our recent work suggests that parkin regulates the turnover of proteins in brain mitochondria and the ability of mitochondria to produce energy. Because mitochondrial stress -- suboptimal conditions that can damage mitochondria -- is linked to PD, we will study the consequences of parkin activation in pre-clinical models with Parkinson's features such as mitochondrial stress. This will allow us to clarify if parkin can protect mitochondria and regulate mitochondrial protein production. We will determine whether activated parkin affects mitochondrial DNA or proteins to accomplish that. We will also study how changes in parkin (its shortage, excess or activation) affect mitochondrial stress.

Importance of this Research for the Development of a New PD Therapy:
This study will help up better understand how parkin protects the cell and reveal the therapeutic potential of parkin. It will also explain how parkin controls the removal of damaged mitochondria from the cell and how it can be used as a target for PD therapies in the future.


Researchers

  • Howard Steven Fox, MD, PhD

    Omaha, NE United States


  • Kelly Lynn Stauch, PhD

    Omaha, NE United States


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