Marine ophiobolin MHO7 binds VDAC2 and drives its loss in triple-negative breast cancer cells
- Activity-based protein profiling flagged VDAC2 as a main interactor of the marine natural product MHO7 in TNBC cells; pull-down, thermal-shift and thermophoresis assays agreed, and cysteine mutants dampened the response.
- MHO7 lowered VDAC2 levels more than VDAC1 or VDAC3 and sped its turnover, with autophagy machinery and p62 contributing.
- Losing VDAC2 altered mitochondria–ER contacts, calcium handling and mitochondrial ROS, though several MHO7 effects persisted after partial depletion.
💡 Points Based on the abstract
That last point is the catch: effects surviving VDAC2 knockdown mean MHO7 is probably polypharmacological, which is normal for an electrophilic terpenoid and a problem for calling VDAC2 'the target'. A clean test is a Cys-mutant VDAC2 knock-in that blocks binding yet keeps the phenotype or loses it. Without in vivo exposure data, this is a target hypothesis, not yet a lead.