Mitochondrial permeability transition (MPT) is a phenomenon characterized by an increase in the permeability of inner mitochondrial membrane. It can cause mitochondrial swelling and subsequent rupture of outer and inner membrane, which lead to release of various mitochondrial components including mitochondrial DNA (mtDNA) that act as a mitochondrial damage-associated molecular pattern. Here we aimed to determine the release of mitochondrial molecules after MPT induction. After hepatotoxic drug-induced MPT, release of mtDNA was observed; it was more significant in db/db mice, an obesity-associated type 2 diabetes (T2D) model. In addition to mtDNA, caspase-dependent or -independent proapoptotic intermembrane space proteins such as endonuclease G, HtrA2/Omi, apoptosis-inducing factor and cytochrome c were also detected in the supernatant of hepatotoxic drug-treated mitochondria from db/db mice. Furthermore, using gene ontology information, we identified that other immune response-associated molecules were released upon induction of MPT. Thus, in obese T2D, MPT-inducing drugs may increase the risk of DILI.
