Mitochondrial cytochrome c release is caspase-dependent and does not involve mitochondrial permeability transition in didemnin b-induced apoptosis

Abstract

Permeability transition, and a subsequent drop in mitochondrial membrane potential (Δψm), have been suggested to be mechanisms by which cytochrome c is released from the mitochondria into the cytosol during apoptosis. Furthermore, a drop in Δψm has been suggested to be an obligate early step in the apoptotic pathway. Didemnin B, a branched cyclic peptolide described to have immunosuppressive, anti-tumour, and anti-viral properties, induces rapid apoptosis in a range of mammalian cell lines. Induction of apoptosis by didemnin B in cultured human pro-myeloid HL-60 cells is the fastest and most complete ever described with all cells being apoptotic after 3 h of treatment. By utilizing the syste..