Title: Effects of Mitochondrial Complex I Activity on Metabolism from in vitro to in vivo
Abstract: NADH provides electrons for aerobic ATP production. In cells with impaired mitochondrial complex I activity, NADH accumulation can be toxic. To minimize such toxicity, elevated NADH inhibits the classical NADH producing pathways: glucose, glutamine, and fatty acid oxidation. Here, through deuterium tracing studies in cultured cells and mice, we show that folate dependent serine catabolism also produces substantial NADH. Strikingly, when
Xi Chen (Troyanskaya Lab)
"Tissue-specific enhancer functional networks for associating distal regulatory regions to disease"
The heme enzyme indoleamine 2.3-dioxygenase (IDO1) regulates the immune response through the oxidation and depletion of tryptophan to produce N-formylkynurenine, in the first committed step of the kynurenine pathway. By depleting the local tissue environment of tryptophan, IDO1 activity stalls the proliferation of T-cells and promotes their conversion to T-regulatory cells, an effect further enhanced by downstream kynurenine products.