Figure 2.

Anticancer therapy (CTx) alters intracellular mitochondrial signaling. Several CTx agents induce mitochondrial dysfunction by promoting mitochondrial DNA (mtDNA) damage, suppressing mitochondrial metabolism, altering mitochondrial Ca²⁺ homeostasis, increasing production of reactive oxygen species (ROS), altering mitochondrial-nuclear communication, and/or inducing epigenetic and transcriptional remodeling. Mitochondria also play a role in CTx-induced apoptosis through release of cytochrome-c (Cyt c) and second mitochondria-derived activator of caspases (SMAC) and activation of apoptosomes. Nucleic acids in the cytosol, including _mtRNA and _mtDNA, activate innate immune cascades that ultimately promote inflammation. Image created with Biorender.com and published with permission. AIM2, absent-in melanoma 2; cGAS, GMP-AMP synthase; IRF3, interferon regulatory factor 3; RIG-I, retinoic acid-inducible gene I; STING, stimulator of interferon genes.