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.