Final Report Summary - METABOMIT (Metabolic consequences of mitochondrial dysfunction)
The MetaboMIT project aimed to discover the consequences of mitochondrial dysfunction for metabolism in different tissues. Our evidence indicates that mitochondria are in tight communication with nutrient intake, and that this communication is guided by B-vitamins, especially B3 (niacin) and B9 (folate), with potential for mitochondrial disease interventions. In stem cell compartment, oxygen radical signaling is key for stem cell commitment, and both overproduction of reactive oxygen species and strong antioxidants can harm the stem cell pool, especially neural stem cells. Furthermore, we showed that mitochondrial dysfunction can remodel cytoplasmic biosynthesis pathways, including transsulfuration, methyl cycle and nucleotide pools, showing that dysfunction within an organelle can have widespread consequences for the whole cell homeostasis. The results open new understanding for mechanisms of aging, obesity and stem cell maintenance.