Alpha-ketoglutarate for adipose tissue rejuvenation

摘要

Alpha-ketoglutarate (aKG), also called 2-oxoglutarate, is an intermediate of the TCA cycle in mitochondria. The mitochondrial membrane is highly permeable to aKG, which is mediated by malate/aKG and aspartate/glutamate exchangers located on mitochondrial membrane, which supplies aKG in the cytoplasm. In addition, aKG is also produced through oxidative deamination of glutamate and glutamine in cytosol. As a key metabolite, aKG is required for catalytic reaction of ten eleven translocation (TET) family of proteins, and TETs convert 5-methyl-cytosine (5mC) to 5-hydroxy-methyl-cytosine (5hmC), a key step in active DNA demethylation in an aKG-dependent manner [ ]. In addition, aKG is also required for histone demethylation mediated by JmjC domain-containing histone demethylases, which catalyze the removal of repressive histone methylation marks (H3K9me3 and H3K27me3) and activate the expression of key developmental genes during stem cell differentiation [ ].