January 23, 2004

The Generation of Reactive Oxygen Species (ROS) in
Heart Mitochondria of Bulls and Mice
Christopher Martinez

MIRT Program
MRC Dunn Human Nutrition Unit, Hills Road, Cambridge

Oxidative phosphorylation is the process by which the
cell makes ATP, the energy used by the cell. This is
accomplished in an organelle known as the powerhouse
of the cell, mitochondria. Mitochondria produce ATP by
allowing electrons to flow from reductants to oxidants
in the electron transport chain. At each complex in
this chain is a hydrogen (or proton) pump which
transfers hydrogen from one side of the membrane to
the other. This creates a gradient across the inner
membrane with a higher concentration of hydrogen ions
in the inter-cristae space. It is this gradient that
facilitates the formation of ATP. It is this process
that is essential to life, but it is also this process
which may be the cause of ageing. During this process
reactive oxygen species (ROS), namely superoxide (O2-
) and peroxide (H2O2), are produced in side reactions.
These ROS are highly reactive and have been shown to
damage DNA. The free radical theory of aging or the
oxidative stress hypothesis states that it is the
mitochondrial production of ROS and the resulting
accumulation of damage to macromolecules that causes
aging and determines maximum lifespan (MLSP). A
prediction of this hypothesis would be that longer-
lived species exhibit a relatively lower level of
oxidative stress due to either a high level of
antioxidant defenses and/or a low rate of oxidant
generation. So do small mammals with short MLSP
produce more ROS than larger mammals with longer
MLSP? But more importantly, if yes than where in the
electron transport chain is the difference in ROS
being produced.