Poster Presenter

Mitochondrial Transporters For Aspartate And Glutamate And Related Diseases
Ferdinando Palmieri
Italy

The inner membranes of mitochondria contain a large family of nuclear-coded proteins that transport a variety of metabolites, nucleotides and coenzymes across the membranes. In man, there are 48 mitochondrial transporters (encoded by the SLC25 genes); about half have been characterized biochemically. Examples are the glutamate carrier and the aspartate/glutamate carrier. In man, both these carriers have two isoforms (GC1/GC2 and AGC1/AGC2, respectively). AGC1 and AGC2 transport L-aspartate, L-glutamate and L-cysteinesulphinate by an obligatory 1:1 exchange; GC1 and GC2 transport only L-glutamate in co-transport with H+ or in exchange for OH-. The activity of AGC1 and AGC2 is stimulated by Ca²⁺ acting on the external side of the inner mitochondrial membrane, and this activation results in increased oxidative metabolism and greater ATP formation in the mitochondrion. AGC is essential for the malate-aspartate cycle and for supplying aspartate from mitochondria to cytosol. GC plays an important role in amino acid degradation and specific cell functions such as ureogenesis. Until now, three autosomal recessive diseases have been found to be caused by defects in one of the AGC or GC isoforms. Type II citrullinemia is due to mutations in SLC25A13 coding AGC2. Alterations in SLC25A12 coding the neuron/muscle-specific isoform AGC1 are responsible for global cerebral hypomyelination. Finally, neonatal epileptic encephalopathy with suppression bursts is caused by mutations in SLC25A22 coding GC1.