Regulation of Ca2+-induced permeability transition by Bcl-2 is antagonized by Drp1 and hFis1 |
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| Authors: | Dejuan Kong Liping Xu Yingjie Yu Weijia Zhu David W Andrews Yisang Yoon Tuan H Kuo |
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| Institution: | (1) Department of Pathology, Wayne State University School of Medicine, Detroit, MI, U.S.A.;(2) Department of Biochemistry, McMaster University, Hamilton, Ontario, Canada;(3) Department of Anesthesiology, and Pharmacology and Physiology, University of Rochester School of Medicine and Dentistry, Rochester, NY, U.S.A.;(4) Department of Pathology, Wayne State University School of Medicine, 540 E. Canfield, Detroit, MI, 48201, U.S.A. |
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| Abstract: | The regulation of mitochondrial permeability transition (MPT) is essential for cell survival. Un-controlled opening of the MPT pore is often associated with cell death. Anti-death protein Bcl-2 can block MPT as assessed by the enhanced capacity of mitochondria to accumulate and retain Ca2+. We report here that two proteins of the mitochondrial fission machinery, dynamin-related protein (Drp1) and human mitochondrial fission protein (hFis1), have an antagonistic effect on Bcl-2. Drp1, with the assistance of hFis1, sensitizes cells to MPT by reducing the mitochondrial Ca2+ retention capacity (CRC). While the reduction of CRC by Drp1/hFis1 is linked to mitochondrial fission, the antagonism between Bcl-2 and Drp1 appears to be mediated by mutually exclusive interactions of the two proteins with hFis1. The complexity of protein–protein interactions demonstrated in the present study suggests that in addition to the previously described role of Bcl-2 in the control of apoptosis, Bcl-2 may also participate directly or indirectly in the regulation of mitochondrial fission. |
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| Keywords: | mitochondria permeability transition Bcl-2 Drp1 hFis1 mitochondrial fission apotosis calcium |
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