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Defects in mitochondria, cells’ internal power packs, further linked to Parkinson’s in Stanford study

New research suggests that targeting mitochondria could be a way to treat Parkinson's disease.

Defective architecture in the nanoscopic power plants that provide energy to every cell in our bodies may underlie the movement difficulties of Parkinson's disease, a new study by Stanford neuroscientist Xinnan Wang, MD, and her associates suggests.

Parkinson's disease, the second-leading neurodegenerative disorder after Alzheimer’s disease, is precipitated by a massive die-off of a set of hard-working, energy-gluttonous midbrain nerve cells whose nonstop activity fine-tunes our voluntary movements.

These nerve cells' voracious energy consumption demands that their tiny internal power plants, called mitochondria, be in the right place at the right time within a cell in order to provide the energy-packing chemicals needed for continued function – and that they be in top working condition at all times.

As for the first requirement, we're fortunate in that mitochondria know how to get around inside a cell. They're quite mobile and have a knack for going where they're needed. But the second requirement is crucial, too. Given the massive energy requirements of those aforementioned midbrain nerve cells, even minor mitochondrial defects can cause a catastrophe.

That's precisely what happened when Wang and her colleagues experimentally messed around with an enzyme called PINK1 that's critical to mitochondrial function. It's already known that mutations in this enzyme can cause early-onset Parkinson's in people.

Evolution being famously parsimonious, fruit flies and people – who diverged from some undoubtedly weird-looking common ancestor at least a zillion years ago – continue to share many things in common. Among those things is that midbrain nerve circuit that controls voluntary movement – it works the same way as ours, and uses essentially the same equipment to do so. That makes fruit flies a great model system for understanding how some of our own deficiencies come about.

And sure enough, preventing PINK1 from doing its job in the flies' mitochondria (by gumming up another mitochondrial enzyme in such a way that PINK1 couldn't perform a necessary operation on that enzyme to make it work) significantly impaired the ability of their larvae to crawl around and, in many cases, led to severe lethality among adult flies.

"We found that PINK1 is required only in highly energetic regions of the cells," Wang told me about her study, which appears in Molecular Cell. "This supports the theory that Parkinson's disease involves local energy shortages inside cells due to mitochochondrial malfunction – and it indicates that targeting mitochondria may have great potential for exploring new therapeutic interventions in Parkinson's."

(An earlier study by Wang and her peers also points to the likely involvement of mitochondrial underperformance in Parkinson's.)

Current treatments for the condition can mitigate symptoms, but they don't appear to stop the steady degeneration of the collection of voluntary-motion-regulating midbrain nerve cells, called the niagrostriatal tract. Maybe treatments that preserve or restore mitochondrial energy production will.

Image of mitochondria by Odra Noel

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