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My name is Christopher Perry.
I am an Associate Professor in
the School of Kinesiology and
Health Science and Director
of the Muscle Health
Research Center at
York University in
Toronto, Canada.
This lecture will provide
an introduction to
the principals of mitochondrial
targeted pharmaceuticals.
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The lecture will first
provide an overview of
various mitochondrial
functions as well as
an example of how
mitochondrial derived signals
can serve as a means of
communication
throughout the cell.
Following this,
mitochondrial responses
to stress signals
will be described.
With this foundational knowledge
an overview of mitochondrial
therapeutics will be provided
with specific examples of
pre-clinical and
clinical research
in various disease states.
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Many cellular processes are
powered by energy
that is shuttled by
the adenylate known as ATP
or adenosine triphosphate.
ATP utilizing proteins
hydrolyze ATP into ADP,
or adenosine diphosphate,
by removing a phosphate.
Mitochondria synthesize ATP by
re-phosphorylating
this ADP through
a process known as
oxidative phosphorylation
given oxygen
is required for this process.
Briefly, nutrients derived from
our food or stored
in cells throughout
our bodies are catabolized
through specific
enzymatic pathways.
This process transfers
electrons from
nutrients such as
glucose, fatty acids,
and amino acids to
electron carriers or
reducing equivalents
known as NADH and FADH2.
Those terms are correct once
they have received
the electrons.
Electrons are transferred from
these reducing equivalents to
specific protein complexes in
the mitochondrial
electron transport chain
also known as the electron
transport system.
Electrons flow from
one component to the
next throughout the
system by following
a path of increasing
redox potentials whereby
each component has a
greater potential to
accept an electron than
the previous component.
Oxygen is the final
electron acceptor
as you will see on the
right by complex 4.
As electrons flow
through this system,
protons are pumped
from the matrix to
the intermembrane space
through complexes 1,
3, and 4.
The accumulation of protons
generates a charge differential
relative to the matrix thereby
creating the proton
motive force.
This differential drives the
re-entry of protons
into the matrix through
ATP synthase thereby powering
the phosphorylation
of ADP into ATP.
Electron transfer to oxygen
at complex 4 produces water.
