Redox-State-Mediated Regulation of Cytochrome c Release in Apoptosis Revealed by Surface-Enhanced Raman Scattering on Nickel Substrates

The interaction of cytochrome c (Cyt c) with cardiolipin (CL) is believed to play an important role in the initial events of apoptosis. Herein, we investigate the structural changes of CL-bound Fe(2+)Cyt c and the correlation with Cyt c release through surface-enhanced Raman spectroscopy (SERS) on nickel substrates. The SERS results together with molecular dynamics simulation reveal that Fe(2+)Cyt c undergoes autoxidation and a relatively larger conformational alteration after binding with CL, inducing higher peroxidase activity of Cyt c and higher permeability of the CL membrane compared with those induced by the Fe(3+)Cyt c. The proapoptotic activity and SERS effect of the Ni nanostructures allow the in situ study of the redox-state-dependent Cyt c release from isolated mitochondria, which reveals for the first time that the ferrous state of Cyt c most likely plays a more important role in triggering apoptosis.