biostudies-literatureMa YBLRD VANIA NIH HHSNIDDK NIH HHSNIAAA NIH HHSNCI NIH HHSNational Institutes of HealthU.S. Department of Veterans Affairs20989-20997https://www.ebi.ac.uk/biostudies/studies/S-EPMC5743073biostudies-literatureUnknown292(51)Dineolignans manassantin A and B from the plant <i>Saururus cernuus</i> are used in traditional medicine to manage a wide range of ailments such as edema, jaundice, and gonorrhea. Cell-based studies have identified several molecular target candidates of manassantin including NF-κB, MAPK, STAT3, and hypoxia-inducible factor 1α (HIF-1α). It is unclear whether or how these structurally diverse proteins or pathways mediate any of the medical benefits of manassantin <i>in vivo</i> Moreover, it has recently been reported that manassantin causes developmental arrest in zebrafish by inhibiting the mitochondrial complex I, but it is unknown whether manassantin inhibits mitochondrial respiration in intact mammalian cells and live animals. Here, we present direct evidence that manassantin potently anThe Journal of biological chemistryThe lignan manassantin is a potent and specific inhibitor of mitochondrial complex I and bioenergetic activity in mammals.PMC5743073DK 105961DK AA 20758R01 DK1059612IO1BX001355-01A2I01 BX001355R21 AG054975P30 CA016059R01 AA020758Hawkridge AMLesnefsky EJFang XChen QMa YMohsin AAWang WOh USanyal AMin HKfalseThe lignan manassantin is a potent and specific inhibitor of mitochondrial complex I and bioenergetic activity in mammals.Dineolignans manassantin A and B from the plant <i>Saururus cernuus</i> are used in traditional medicine to manage a wide range of ailments such as edema, jaundice, and gonorrhea. Cell-based studies have identified several molecular target candidates of manassantin including NF-κB, MAPK, STAT3, and hypoxia-inducible factor 1α (HIF-1α). It is unclear whether or how these structurally diverse proteins or pathways mediate any of the medical benefits of manassantin <i>in vivo</i> Moreover, it has recently been reported that manassantin causes developmental arrest in zebrafish by inhibiting the mitochondrial complex I, but it is unknown whether manassantin inhibits mitochondrial respiration in intact mammalian cells and live animals. Here, we present direct evidence that manassantin potently an2017-01-01T00:00:00Z2017 Dec2025-04-19T01:47:01.759Z2019-03-27T00:12:40ZS-EPMC57430732904635210.1074/jbc.m117.81292510.1074/jbc.M117.812925