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Multi-parameter Measurement of the Permeability Transition Pore Opening in Isolated Mouse Heart Mitochondria
Published on: September 7, 2012
mCICR is required for As2O3-induced permeability transition pore opening and cytochrome c release from mitochondria
Xuemei Tian1, Xiaodong Ma, Dongfang Qiao
1Deparment of Histology and Embryology, Southern Medical University, Guangzhou, Guangdong, 510515, China.
Abstract:
The permeability transition pore (PTP) is central for apoptosis by acting as a good candidate pathway for the release of Cyt. c and apoptosis induction factors (AIF). Arsenite induces apoptosis via a direct effect on PTP. To characterize the exact mechanism for arsenite induces PTP opening, the effect of Ca2+ on As2O3-induced PTP opening, the relationship between As2O3-induced PTP opening and Cyt. c release from mitochondria and calcium-induced calcium release from mitochondria (mCICR), and the effects of As2O3 on Ca2+-induced PTP opening were studied. The results showed As2O3 induces Cyt. c release by triggering PTP opening. Ca2+ is necessary for As2O3-induced PTP opening. As2O3-induced PTP opening and Cyt. c release depends on mCICR. As2O3 promotes PTP opening by lowering Ca2+-threshold. These results indicated As2O3 induce Cyt. c release from mitochondria by lowering Ca2+-threshold for PTP and triggering mCICR-dependent PTP opening. Suggesting that it is possible to control apoptosis by altering Ca2+ threshold and mCICR to modulate PTP opening and Cyt. c release.
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