Institution: | (1) National Key Lab of Biomembrane and Membrane Biotechnology, Peking University, 100871 Beijing, China;(2) National Key Lab of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, 100080 Beijing, China;(3) Tianjin Sports Institute, 300381 Tianjin, China |
Abstract: | Caspase-3 plays a central role in the execution of apoptosis. Besides many substrates of caspase-3, mitochondria seem to be one of the candidate targets in the apoptotic process. We evaluated the effects of caspase-3 on the isolated mitochondria in detail, and especially focused on the mechanism involved in mitochondrial functions, which were not fully assessed till now. Our results showed that recombinant caspase-3 induced the increase of superoxide production, the dissipation of mitochondrial membrane potential and rate increasing of mitochondrial state 4 respiration. Caspases inhibitor, z-VAD-fmk can inhibit these effects of caspase-3 on mitochondria. Bcl-xL and cyclosporin A were also shown to be able to inhibit these changes. These results suggested a possible mechanism in caspase-3 induced disruption of mitochondrial membrane barrier which formed a positive feedback loop in apoptosis. |