Background
Glutamate oxaloacetate transaminase 2, a mitochondrial enzyme, catalyzes the conversion of oxaloacetate to aspartate. Studies show that the metabolite pyridoxal phosphate is selectively required by acute myeloid leukemia. PLP-dependent GOT2 selectively sustains leukemic cell proliferation. Depletion of GOT2 suppresses the proliferation of acute myeloid leukemia cells. In addition, mouse hematopoietic stem cells are dependent on cell-autonomous aspartate synthesis. Got2 deletion leads to decreased aspartate levels and reduced hematopoietic stem cell function. Furthermore, GOT2-dependent aspartate synthesis is also necessary for protein and collagen biosynthesis in chondrocytes and is critical for chondrocyte proliferation and growth.
References
[1] Chen, C.C. et al. (2020) Cancer Cell 37, 71-84.e7.
[2] Qi, L. et al. (2021) Cell Stem Cell 28, 1982-1999.e8.
[3] Stegen, S. et al. (2020) Dev Cell 53, 530-544.e8.
