NMS-873 functions as a dual inhibitor of mitochondrial oxidative phosphorylation

In this study we describe our serendipitous discovery that NMS-873, a compound that was previously identified as a highly selective allosteric inhibitor of the ATPase valosin-containing protein (VCP/p97), rapidly induces aerobic fermentation in cultured human and mouse cells. Our further investigation uncovered an unexpected off-target effect of NMS-873 on mitochondrial oxidative phosphorylation, specifically as a dual inhibitor of Complex I and ATP synthase. This work points to the need for caution regarding the interpretation of cell survival data associated with NMS-873 treatment and indicates that cellular toxicity associated with its use may be caused by both VCP/p97-dependent and VCP/p97-independent mechanisms.PMID:33727138 | DOI:10.1016/j.biochi.2021.03.004

Source: Biochimie - March 17, 2021 Category: Biochemistry Authors: Miranda F Bouwer Kathryn E Hamilton Patrick B Jonker Sam R Kuiper Larry L Louters Brendan D Looyenga Source Type: research