Succinate as a mobilization cue
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Succinic acid, being a metabolite of the Krebs cycle and the end product of anaerobic transformations in mitochondria, functions outside mitochondria and cells as a regulatory signal. In the cytosol, micromolar amounts of succinate stabilize the transcriptional hypoxia-inducible factor HIF, which triggers the genes responsible for adaptation to hypoxia. Outside the cells, succinate activates the SUCNR1 receptor, which increases the concentration of intracellular calcium. The effect of short bursts of endogenous succinate accumulation and signaling after hypoxia/ischemia, or extreme glucose use from physical exercise should be distinguished from the effect of a permanently increased level of endogenous succinate under pathology (obesity, diabetes mellitus, chronic ischemia, succinate dehydrogenase damage). A short succinate signal triggers an adaptive response by an organism. Prolonged rise and highly elevated levels of endogenous succinate is a pro-inflammatory, damaging factor that can contribute to the progression of neoplasms. Use of succinate-containing compositions at a dose of 0.5-5 millimole can only provide a short signal. This is due to the positive effect of a number of succinate-containing agents.
Eugene I. Maevsky, Anna A. Vasilyeva, Mikhail V. Kozhurin, Paul Leonard, Polina M. Schwarzburd, Mikhail I. Uchitel, Elena A. Zapatrina, Marina E. Maevskaya, Lyudmila A. Bogdanova. Succinate as a mobilization cue. Cardiometry; Issue 17; November 2020; p.110-120; DOI: 10.12710/cardiometry.2020.17.110120; Available from: http://www.cardiometry.net/issues/no17-november-2020/mobilization-cue