Roles
Professor of Physiology and Biophysics
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Research Interests
We are studying mechanisms that control respiration in adult mammalian spinal motor neurons. Fluorescence imaging techniques are used to measure changes in oxygen consumption, NADH and mitochondrial membrane potential in response to trains of action potentials. NADH (= nicotinamide adenine dinucleotide) is the energy supply for complex I of the mitochondrial electron transport chain, but our data indicate that [NADH] does not usually control the rate of mitochondrial oxygen consumption. Possible explanations for this surprising finding are that there is a reserve supply of NADH that is adequate to support respiration temporarily, and/or that a valve-like mechanism controls the flux of energy from NADH into the chemical potential in the mitochondrial electron transport chain. We are also investigating mechanisms controlling the level of NAD+ in motor neuron mitochondria. The reported half-life of NAD+ in other cells is ~2 hours, but we find a component with half-life of only ~ 20 minutes in motor neurons of mice expressing a mutation that causes a familial form of amyotrophic lateral sclerosis (ALS). We are investigating the cause of this short half-life, which may be linked to the NAD+ deficiency reported in ALS patients. This work is being done in collaboration with Dr. Ellen Barrett. -
Publications
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