Pierre MAECHLER
Mitochondria and metabolic signals.
We study how mitochondria integrate and generate metabolic signals controlling the coupling of glucose recognition to insulin exocytosis. Previous work in permeabilized beta-cells has demonstrated that the mitochondrion is the source of a so far unidentified factor(s) generated by nutrient stimuli. This factor, we identified as being glutamate, participates in the stimulation of insulin secretion. Current work investigates generation, intracellular transport, and mechanism of action of glutamate in beta-cells. In particular, we cloned a new mitochondrial glutamate carrier and investigate the role of aspartate/glutamate carrier in mitochondrial shuttle function. We also study the metabolic effects of patient-derived mitochondrial DNA mutations associated with diabetes. One of the main current projects is the study of transgenic mice with tissue specific (beta cells, liver, brain) knockout of glutamate dehydrogenase.
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(Figures from Nature 414:807-812)
