The title of the talk is "Exercise and Nutrition in Mitochondrial Disorders".
My name is Mark Tarnopolsky.
I'm a Professor of Pediatrics and Medicine at McMaster University in Hamilton, Canada.
What we'll be talking about today is an overview of mitochondrial cytopathies.
Then, we'll go into the diagnostic criteria for mitochondrial cytopathies.
We'll then talk about the consequences of mitochondrial dysfunction.
We'll move then into exercise therapy in mitochondrial disease and
finish with nutrition and nutraceutical therapies for mitochondrial disorders.
The mitochondria were thought to be
originally a purple photosynthetic bacteria which
invaded a protoeukaryotic cell about 1.5 billion years ago.
At the time, it was estimated that
approximately 1300 genes were used to encode for these bacteria.
Throughout the course of evolution,
there's been a sharing of the genetic material whereby
the original genetic material in the bacteria
is retained at something called the mitochondrial DNA.
This contains 37 genes.
Now, most of the proteins which encode for the bacteria,
now called the mitochondria,
are done so through the nuclear DNA.
In addition to the 22,000 genes that encode for other proteins,
1300 now encode for mitochondrial proteins.
The mitochondria are the main site for intermediary oxidative metabolism of fats,
proteins, and carbohydrates through the electron transport chain,
which we'll discuss in just a minute.
These are also important in apoptosis,
which is preprogrammed cell death,
the production of reactive oxygen species,
activation of the inflammasome,
and it's even been linked to aging through telomere length.
This slide shows the classic electron transport chain.
So, what we have here are essentially
the reducing equivalents from food used to provide substrates namely,
NADH plus H+
or succinate, or FADH2.
The potential energy is provided to Complex I and Complex II.
What happens is that this energy is used to move electrons along the respiratory chain,
which ultimately then reduces molecular oxygen to water at Complex IV.
But this energy is used to pump the protons,
which you can see at Complex I, III, and IV,
from the matrix of the mitochondria to the intermembrane space.
That potential energy is then used at Complex V to flow
back through the proton-motive force to rephosphorylate ADP back to ATP.
You can also see here, depicted in color,
those are the subunits of
the various respiratory chain complexes that are encoded for by mitochondrial DNA,
and the majority of them as you can see in gray are encoded for by the nuclear DNA.
This forms a series circuit essentially between Complex I,
III, IV, which is highly conserved throughout all of the vertebrate.
You can also see here coenzyme Q10,
which receives the electrons from both Complex I and Complex II.
And later on, we'll see that coenzyme Q10 is one of the therapeutic targets.