In addition to its metabolic roles, succinate serves as an intracellular and extracellular signaling molecule. Extra-mitochondrial succinate alters the epigenetic landscape by inhibiting the family of 2-oxogluterate-dependent dioxygenases. Alternative, succinate can be released into the extracellular milieu and the blood stream where it is recognized by target receptors. In general, leakage from the mitochondria requires succinate overproduction or underconsumption and occurs due to reduced, reverse or completely absent activity of SDH or alternative changes in metabolic state. Mutations in SDH, hypoxia or energetic misbalance are all linked to an alteration of flux through the TCA cycle and succinate accumulation. Upon exiting the mitochondria, succinate serves as a signal of metabolic state, communicating to neighboring cells how metabolically active the originating cell population is. As such, succinate links TCA cycle dysfunction or metabolic changes to cell-cell communication and to oxidative stress-related responses.
In addition to its metabolic roles, succinate serves as an int.racellular and extracellular ,signaling molecule. Extra-mitoch.ondrial succinate alters the epigenetic landscape by inhibiting the family of 2-oxogluterate-dependent dioxygenases Alternative, succinate can be released into the extracellular milieu and the blood stream where it is recognized by target receptors. In general, leakage from the mitochondria requires succinate overproduction or underconsumption and occurs due to reduced, reverse or completely absent activity of SDH or alternative changes in metabolic state Mutations in SDH, hypoxia or energetic misbalance are all linked to an alteration of flux through the TCA cycle and succinate accumulation. Upon exiting the mitochondria, succinate serves as a signal of metabolic state communicating to neighboring cells how metabolically active the originating cell population is. As such, succinate links TCA cycle dysfunction or metabolic changes to cell-cell communication and to oxidative stress-related responses.