My name is David Hood and I'm a professor at York University in Toronto.
I'm the Director of the Muscle Health Research Center,
a center with 22 scientists that study muscle.
Today, I'm going to talk about mitochondrial biogenesis in muscle, part two.
The topics that we'll discuss include
the signalling and mechanisms involved in mitochondrial biogenesis in muscle,
the protein import pathway as
an important component of how mitochondrial reticulum is assembled,
and end the discussion with how aging muscle,
mitochondria respond to exercise.
We know for some time now,
that there are basically
three intracellular signals that lead to the production of more mitochondria,
which we call mitochondria biogenesis.
So, this image is of a cartoon of a muscle fiber.
You can see the neuromuscular junction leads to
activation of the muscle calcium release from the sarcoplamic reticulum.
That acts as one of the signals.
Calcium activating kinases, like CaM kinase that will affect
transcription of the genes and it's gene transcription that leads to more mRNA.
The mRNA is translated in the cytosol and the proteins are made.
Some of those proteins will return back to the nucleus,
to act as transcription factor,
but others will enter the mitochondrion through a sophisticated protein import machinery.
That contributes to the biogenesis of
mitochondria as we'll say more about in a few minutes.
When muscle contracts in response to an electrical impulse at the neuromuscular junction,
we get depolarization who break down ATP, ATP to ADP,
some of that ADP is converted to AMP,
and that activates AMP kinase,
which is the second signalling kinase which can also impact transcription.
So, calcium is one signal,
AMP kinase activation is a second signal.
The third signal is the production of reactive oxygen species,
or ROS in this image,
which can come from mitochondria,
come from other reactive oxygen species, enzymes as well.
Those reactive oxygen species also act as
a third signal that leads to transcription in the nucleus
to affect a number of mitochondrial proteins that in
turn influences mitochondrial content in the muscle.
Those are the three signals we believe respond to exercise.
I'll show you some evidence for each of the two signals calcium
first and then AMP kinase activation in subsequent slides.