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mCICR is required for As2O3-induced permeability transition pore opening and cytochrome c release from mitochondria

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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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Authors and Affiliations

  1. Deparment of Histology and Embryology, Southern Medical University, Guangzhou, Guangdong, 510515, China

    Xuemei Tian & Fang Yan

  2. Central Laboratory, Southern Medical University, Guangzhou, Guangdong, China

    Xiaodong Ma, Dongfang Qiao, Ande Ma & Xingxu Huang

  3. Deparment of Histology and Embryology, Central Laboratory, Southern Medical University, Guangzhou, Guangdong, 510515, China

    Xingxu Huang

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  1. Xuemei Tian
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Correspondence to Xingxu Huang.

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Tian, X., Ma, X., Qiao, D. et al. mCICR is required for As2O3-induced permeability transition pore opening and cytochrome c release from mitochondria. Mol Cell Biochem 277, 33–42 (2005). https://doi.org/10.1007/s11010-005-4818-x

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  • DOI: https://doi.org/10.1007/s11010-005-4818-x

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