Study on the relationship between calcium-induced calcium release from mitochondria and PTP opening

The permeability transition pore (PTP) is central for mitochondria function. PTP either open in low-conductance state to carry out mCICR (Ca²⁺-induced Ca²⁺ release from mitochondria) and play roles in cell phsyiological activities or open in high-conductance conformation to release harmful substances and play important roles in cell pathological responses and apoptosis. The results of study on the relationship between mCICR and PTP opening show Ca²⁺ concentrations but not the Ca²⁺ delivery mode determined the occurrence of mCICR or PTP opening. Ca²⁺-induced PTP opening began with and depended on mCICR. mCICR was a prerequisite for H₂O₂ and As₂O₃-induced PTP opening. The results indicated that the PTP opening was determined by Ca²⁺ stimulation intensity but not mode. PTP could switch from low- to high-conductance conformation and the PTP open by high-conductance began with low-conductance state. mCICR is necessary for Ca²⁺-dependent PTP opening. Our data suggested also that it would be possible to control cellular responses first by modulating mCICR, then by regulating PTP opening.