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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 principles 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 preclinical 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
rephosphorylating 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 IV.
As electrons flow
through this system,
protons are pumped
from the matrix to
the intermembrane space through
Complexes I, III, and IV.
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 IV produces water.
