Bid BH3 peptide, but not its mutant form G 94 E, induces permeability transition pore opening and cytochrome c release 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 G 94 E, 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 (Ψ m ) and cyt c release from mitochondrial in vitro. PTP opening and the loss of Ψ m were inhibited by Bcl-xL, cyclosporin A and ruthenium red, and the latter was an inhibitor of Ca 2+ uniporter in the mitochondrial membrane. These results indicate that Bid BH3 peptide could antagonize Bcl-xL to induced PTP opening and mitochondrial dysfunction.