Uncovering how an alternative mitochondria cleanup process may reduce brain inflammation
Inflammation is the body’s way of dealing with unwanted invaders, mobilizing immune cells to contain, destroy, and clean up areas of infection or injury. However, this process sometimes malfunctions, leading to cell and tissue damage. There is evidence to suggest that such inflammation misfires occur in Parkinson’s disease (PD) and may be contributing to neuron degeneration; however, the source of these potential inflammatory errors has not yet been identified. Tahnee Saunders, PhD, recipient of a Parkinson’s Foundation Postdoctoral Fellowship for Basic Scientists, believes that answer may lie in mitochondria, the powerhouses of the cell.
Mitochondria are organelles, or “mini organs,” found in nearly all cells that use oxygen to power numerous critical biological processes. Like any other hard-working engines, mitochondria eventually get worn out and may break down, requiring disposal by the cell in a process called mitophagy (from the Latin “phagus”, meaning “to eat”) that involves the proteins PINK1 and Parkin. In some cases of young-onset PD, those two mitophagy proteins are dysfunctional, preventing the disposal of broken mitochondria and potentially contributing to increased inflammation and neurodegeneration.
Dr. Saunders, working with her colleagues in the lab of Associate Professor Michael Lazarou at the Walter and Eliza Hall Institute in Victoria, Australia, will be investigating a new form of mitophagy that may hold therapeutic promise for those with PD involving mitochondrial damage. This form of mitophagy occurs when the inner mitochondrial membrane (IMM) becomes exposed and is used to start the disposal chain reaction independent of PINK1 and Parkin. Using cells from both PD-model mice and from people with PD, Dr. Saunders will define the key factors driving IMM-induced mitophagy while also exploring the prevalence of this pathway in different cell types found in the brain.
With the knowledge gained from this research, novel therapies may be developed that boost IMM-induced mitophagy in the brains of those with PD, including individuals with PINK1 or Parkin deficiencies, potentially reducing inflammation and consequent neuron loss. Such therapies could one day be life-changing to those with PD, slowing or even stopping the progression of the disease.
When asked what this Parkinson’s Foundation grant award means to her, Dr. Saunders said it “has been a huge validation of the work I am doing and has given me a clear vision for my future research into Parkinson’s disease…I feel extremely passionate about helping those living with Parkinson’s.”
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