Functional Impact of Nth-like DNA glycosylase on Mitochondrial Dynamics

As a consequence, NTHL1-knockout cells showed resistance to MPP+-induced mitochondrial stress along with increased phosphorylation of eIF2α. Together, this suggests that the loss of NTHL1 may enhance the cell's resilience to oxidative stress resilience by activating protective integrated stress response and mitohormesis pathways thereby contributing to cellular survival under adverse conditions. Collectively, our findings position NTHL1 as a key player in mtDNA stability and mitochondrial resilience, linking its DNA repair activity to mitochondrial resilience and underscoring its broader role in cellular health.

Its loss triggers a shift from canonical oxidative phosphorylation to stress-adaptive pathways, ultimately enhancing cellular resilience against oxidative stress through the activation of the mitochondrial hormetic response.