2.2.8 Mitochondrial deacetylase sirtuin-3 (SIRT3)
Kavita Bhalla et al 49 found elevated activity of the mitochondrial deacetylase sirtuin-3 (SIRT3) in diffuse B-cell lymphoma (DLBCL) triggered via ATM deficiency, resulting in altered mitochondrial structure, lowered TCA flux, and enrichment of the glutamate receptor and glutamine pathways. ATM kinases are vital regulators of the DNA damage response, and B-cell tumors with ATM-zero phenotype mitochondria are poorly dealt with and do no longer respond to either traditional cures or DNA damaging drugs. In the absence of DDR, ATM prompts in response to mitochondrial oxidative stress 50. Mitochondrial structures are swollen in ATM mutant DLBCL cells, and SIRT3 stimulation does not reverse the structural changes in mitochondria but can repair cell proliferation of DLBCL with CRISPR knockout ATM.