The stress-sensing MARCH5 axis governs blood cancer apoptotic resilience via tractable protein-protein interactions

This study investigates the role of the mitochondrial E3 ligase MARCH5 in regulating apoptotic resilience in blood cancers, particularly acute myeloid leukemia and myeloma. The authors demonstrate that MARCH5 forms a stress-sensing complex at mitochondria-ER contact sites, which modulates apoptosis in response to organellar damage and influences the sensitivity of cancer cells to BCL-2 and BCL-XL inhibitors. The findings suggest that targeting specific protein-protein interactions within this complex could enhance therapeutic responses in resistant blood cancer cells.