ZCM-I-1 is a selective small molecule modulator modulator of the production of reactive oxygen species (ROS) from mitochondrial complex I, does not alter mitochondrial membrane potential and bioenergetics, selectively targets mitochondrial complex I via interactions with the IF site.
ZCM-I-1 dose-dependently suppresses mitoROS production as measured by mitoSOX fluorescence, suppresses the production of mitoROS induced by rotenone.
ZCM-I-1 dose dependently reverses mitochondrial depolarization induced by MPP+, a known complex I inhibitor, in both primary mouse cortical neurons and SHSY5Y cells.
ZCM-I-1 has no effects on mitochondrial membrane potential and the level of ATP in MC65 cells, suggesting no effects on the coupling and bioenergetics of mitochondria.
ZCM-I-1 selectively targets mitochondrial complex I via interactions with the IF site.
ZCM-I-1 selectively modulates the respiration of mitochondrial complex I in in isolated mitochondria from the cerebral cortex of C57BL/6 mic, modulates the maximal rate of ADP stimulated respiration of pyruvate as the complex I substrate, but not with succinate as the complex II substrate.
ZCM-I-1 (50 mg/kg, oral gavage, 5 times/week) exhibits selective modulation on the respiration in in vivo using transgenic AD mice since mitochondrial dysfunction.