Nagi Mahammadzade, Sadig Niftullayev
Abstract
Mitochondria is an energy-generating organelle that contains its own genetic material mitochondrial DNA (mtDNA). Although strictly confined within the mitochondrial network, mtDNA sometimes escapes from this confinement to the cytoplasm. Since such mtDNA escape has serious influences on different cellular pathways, it is important to understand the underlying mechanisms and consequences of this process. In order to understand the mtDNA leakage phenomenon better, in this article, we review the research that explores unique features of mitochondria, including its origin, nuclear gene transfer, and different escape mechanisms. Notably, we highlight the Bax/Bak-dependent and VDAC-dependent escape of the mtDNA into the cytoplasm and subsequent activation of the cGAS/STING pathway. Several studies suggest that Bax/Bak pores and VDAC channels are active under extreme and moderate stress levels, respectively, and this activation leads to mtDNA leakage to the cytoplasm. Further investigations have to be conducted to have a more comprehensive view of the flow of mtDNA from mitochondria to cytoplasm and possibly even to the nucleus. Given that mitochondrial malfunctioning has been broadly implicated in a myriad of physiological and pathological conditions, mtDNA leakage and its prevention can be a very attractive target for clinical interventions.