The interaction between PINK1 and the Mitochondrial Processing Peptidase
Dr. Karl Grenier | McGill University
$30,000 (2 years) Porridge for Parkinson’s Graduate Student Award
The interaction between PINK1 and the Mitochondrial Processing Peptidase: Defining the role of Mitochondrial import defects in Parkinson’s Disease
Dr. Karl Grenier is an avid scholar, who completed a bachelor degree in biotechnology and a PhD in Neuroscience prior to embarking on the medical profession journey. His research interests include mitochondrial biology, organoids as prognosticating tools in medicine and mast cells in physiology and disease, while his clinical interests reside in pediatric and perinatal pathology, neuropathology and molecular pathology.
Dr. Grenier was the recipient of the Porridge for Parkinson’s 2013 Graduate Student Award. His PhD studies focused on neurodegeneration mechanisms in PD. Specifically, he helped identify the nature of the protein that helps stabilize PINK1, and his results provided a novel view of how PINK1 is imported into the mitochondria. These novel results give us essential information on how the loss-of-function of PINK1 might lead to neuronal death by knowing where PINK1 is and what important role it plays in the cell.
Substantial progress was made on understanding how PINK1 contributes to mitochondrial quality control and adds essential information to a pathway that is now a primary suspect in causing Parkinson’s disease.
More about Karl's research
Karl Grenier vividly recalls his first encounter with Parkinson’s disease at six years of age, when he was convinced he might be suffering from this illness.
I was watching a television documentary about it, and afterwards I was crying when I went downstairs to see my Mom,” he says. “I had been looking at my hands and they had the slightest of movements, so I told her I had Parkinson’s disease. – Dr. Grenier
She assured him these movements were perfectly normal. Even more importantly, she told him that if he maintained an interest in the problem, he could eventually find a way to help people who did have Parkinson’s disease. Today, more than 20 years later, he is doing just that.
Grenier launched his Porridge for Parkinson’s (Toronto) supported project examining two proteins that help our body’s cells deal with damaged components. One of those proteins is responsible for detecting trouble within a cell when the structure that provides energy to the cell breaks down. If that happens, the second protein takes over and eliminates this structure before it becomes toxic, poisoning the rest of the cell.
When these proteins function properly, this process of detection and disposal takes place all the time. But when they stop doing their job, cells become contaminated by waste products until they can no longer operate. When those cells are in the brain, the effect sets the stage for Parkinson’s disease.
The research conducted as part of this Graduate Student Award offered significant findings. Specifically, Dr. Grenier successfully identified the nature of the protein that helps stabilize the protein PINK1, and identified a previously unknown route by which PINK1 is imported into the mitochondria. These novel results provide essential information on how the loss-of-function of PINK1 might lead to cell death.
The biggest impact of this research is that it provides fundamental knowledge on neurodegeneration mechanisms in Parkinson’s. The results directly contribute to the understanding of what goes wrong in neurons before they start to die. Specifically, the results provide a new viewpoint as to how PINK1 interacts with the mitochondrial import machinery and adds essential information to a pathway that is now a primary suspect in causing Parkinson’s.
With a better understanding of how these proteins work, it should be possible to design drugs to restore their function and stop the disease at the cellular level. In the meantime, Grenier is grateful for the opportunity to acquire such an understanding, provided through the Porridge for Parkinson’s (Toronto) Graduate Student Award.
Grenier noted his gratitude to Porridge for Parkinson’s supporters “In the first few years of my PhD I learned a lot, but things are really coming together now,” he says. “This is where you make most of your discoveries, and it’s key to have someone to support you when things matter most.”
Grenier, Karl (2015). Characterization of PINK1 processing and import into the mitochondrion and of its role in mitophagy (https://escholarship.mcgill.ca/concern/theses/6t053k245) [Doctoral dissertation, McGill University, Montreal]. eScholarship, McGill.