Bid BH3 peptide, but not its mutant form G94E, induces permeability transition poreopening and cytochrome crelease in vitro

It has been shown that Bid and its truncated form tBid could induce cytochrome c (cyt c) release without impacting on PTP. We first show that Bid BH3 peptide, but not its mutant form of Bid BH3 peptide G94E, which is unable to bind to Bcl-xL, induces permeability transition pore (PTP) opening in a dose dependent manner. Bid BH3 peptide also induces the reduction of mitochondria membrane potential (ψm) and cyt c release from mitochondrial in vitro.PTP opening and the loss of ψm were inhibited by Bcl-xL,cyclosporin A and ruthenium red, and the latter was an inhibitor of Ca2+ uniporter in the mitochondrial membrane.These results indicate that Bid BH3 peptide could antagonize Bcl-xL to induced PTP opening and mitochondrial dysfunction.