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Basic information

Name Kazuma Hamada
Belonging department Department of Pharmaceutical Sciences,Faculty of Pharmaceutical Sciences
Occupation name Associate Professor
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Mitochondrial permeability transition as a trigger of immune-mediated drug-induced liver injury in obese type 2 diabetes

Sole or Joint Author


Date of Issue


Conference Presentation(name)

The 28th Annual Meeting of JSIT, Sept, 2021


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.