Author: Shelley Schlender

. . . Short Feature from this week’s How on Earth:

Parkinson’s and Mitochondria (6 minutes)

EDITOR’S NOTE:  The written version below includes further clarifications from Emory scientist Zixu Mao:

We all know about how our blood can give clues about our health, and disease.  But it turns out levels of some health markers aren’t always evident just by looking in the blood.  Inside a cell, some substances can be higher, or lower.  That’s true, for instance, for calcium.  For sugar.  And even for something such as uric acid.  So scientists have been figuring out better ways to check the amounts of these substances not just in our blood, but INSIDE our cells.  The need to look closely doesn’t stop there–it can extend to the organelles within the cells.  And researchers at Emory University School of Medicine have just made a breakthrough about why to look inside these tiny components of a cell.  Their discovery involves a disease made famous by Michael J. Fox.   It’s Parkinson’s, also known as, “The Shaking Disease.”  And the thing inside a cell — which needs to be monitored — is mitochondria.   Mitochondria are often called the miniature power plants within our cells.  But they do much more, according to Zixu Mao, a researcher at Emory University School of Medicine who’s been studying mitochondria and Parkinson’s.  Mao says if mitochondria are sick, the entire cell can be sick.

MAO
If mitochondria disfunction, it sends out signals to the rest of the cell and may even execute cell death.  In addition to that if mitochondria is disrupted, it produces toxic signals to cells that stress cells.  That’s oxidative stress.  So it does multiple things.

In other words, if enough mitochondria are sick, not only does the cell lack energy . . . the mitochondria can generate signals that range from stressing the cell to directing the cell to kill itself.

One protein that helps cells deal with stress is called MEF2-D.  MEF2-D is important, because it helps protect a cell’s DNA from damage when oxidative stress starts going high.  Many researchers have believed that inside our cells, healthy levels of MEF2-D, and healthy mitochondria, both play a role in reducing the chance of Parkinson’s disease.  But there’s been a puzzle, because sometimes, people have Parkinson’s even when they have adequate levels of MEF2-D inside their cells.

That’s where Mao’s team has made a breakthrough, and their breakthrough came from a basic understanding of those tiny cellular power-stations, the mitochondria.  You see, mitochondria are actually tiny cells themselves that, billions of years ago, took up residence inside our cells.  It’s a great team – our cells give mitochondria food and a safe place to live, and in return, the mitochondria generate easy-to-use energy for the cell.  There’s plenty that’s interesting about a mitochondria.

A key thing that interested Mao’s team is that mitochondria have their own DNA that’s distinct from the larger cell’s nuclear DNA.  Because MEF2-D affects the health of the larger cell’s DNA, the Emory researchers wondered whether MEF2-D might play a role in the mitochondria’s DNA.  This was a new idea, because scientists have generally assumed that MEF2-D is only important for the nuclear DNA.

It took meticulous lab work to figure out, but Mao’s team did discover that MEF2-D is, indeed, inside the mitochondria.  What’s more, levels in the mitochondria can be deficient — even when MEF2-D is abundant in other areas of the cell.  As further evidence of a link to disease, Mao’s team documented that certain pesticides and illegal drugs known to increase the risk of Parkinson’s also reduce the level of MEF2-D inside the mitochondria . . . even when the level of MEF2-D is normal in the rest of the cell.  So it’s looking like MEF2-D, in the mitochondria, may be a strong signal about Parkinson’s.

Mao says that right now, it’s too early to use this new-found knowledge for diagnostic purposes.  But he says it does have potential, and someday, instead of requiring complicated work in a science lab, it might even be possible to check the mitochondrial MEF-2D levels by going to a clinic and giving a tube of blood.

MAO
We did some unpublished work and we showed that we could take a patient’s blood and isolate the white blood cells from patients, then isolate the mitochondria from white blood cells and take the MEF2-D in that prep.
There’s more to work out, involving the network of problems that may link levels of MEF2-D in the mitochondria to the shaking disease known as Parkinson’s.  As for when this surprising new signal about cell health might lead to a blood test for disease, Mao says this:

MAO
I have no idea!  But we are working very hard at it.  We know it’s there.  We can detect it.  The hurdle next is to link its change to specific pathological situations.  And that’s a much harder task, I think.

It’s a harder task to do, but if Mao and his team succeed, they might unlock clues about  mitochondrial disorders observed in other neuro-degenerative diseases, plus heart disease, and how these might be linked to MEF2D.  The Emory research about Parkinson’s and mitochondria is published online this week in the Journal of Clinical Investigation.