The dihydrolipoamide acetyltransferase is a novel metabolic longevity factor and is required for calorie restriction-mediated life span extension.

Calorie restriction (CR) extends life span in a wide variety of species. Recent studies suggest that an increase in mitochondrial metabolism mediates CR-induced life span extension. Here we present evidence that Lat1 (dihydrolipoamide acetyltransferase), the E2 component of the mitochondrial pyruvate dehydrogenase complex, is a novel metabolic longevity factor in the CR pathway.

Accounting for strain-specific differences during RTG target gene regulation in Saccharomyces cerevisiae.

Mitochondrial dysfunction results in the expression, via the retrograde response pathway, of a concise set of genes (RTG target genes) that encode enzymes involved in the anapleurotic production of alpha-ketoglutarate. Inhibiting the rapamycin-sensitive TOR kinases, important regulators of cell growth, similarly results in RTG target gene expression under rich nutrient conditions. Retrograde and TOR-dependent regulation of RTG target genes requires a number of shared components, including the heterodimeric bZip/HLH transcription factors Rtg1p and Rtg3p, as well as their upstream regulator Mks1p.

Tor signaling and nutrient-based signals converge on Mks1p phosphorylation to regulate expression of Rtg1.Rtg3p-dependent target genes.

The heterodimeric bZip/HLH transcription factors Rtg1p and Rtg3p regulate the expression of a concise set of metabolic genes (termed RTG target genes) required for de novo biosynthesis of glutamate and glutamine. Several components have now been identified that control both the intracellular localization as well as activity of the Rtg1p.Rtg3p complex, yet the precise upstream regulatory signals involved remain unclear.

Mks1 in concert with TOR signaling negatively regulates RTG target gene expression in S. cerevisiae.

The target of rapamycin (TOR) signaling pathway allows eukaryotic cells to regulate their growth in response to nutritional cues. In S. cerevisiae, TOR controls the expression of genes involved in several nutrient-responsive biosynthetic pathways.