Regulation of Ca2+-induced permeability transition by Bcl-2 is antagonized by Drpl and hFis1.
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.
Kong
Dejuan
D
Department of Pathology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Xu
Liping
L
Yu
Yingjie
Y
Zhu
Weijia
W
Andrews
David W
DW
Yoon
Yisang
Y
Kuo
Tuan H
TH
D000818:Animals; D017209:Apoptosis; D019556:COS Cells; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002413:Cations, Divalent / Q000378:metabolism / Q000494:pharmacology; D002522:Chlorocebus aethiops; D034281:Dynamins; D020558:GTP Phosphohydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010539:Permeability / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors* / Q000378:metabolism
D002413:Cations, Divalent; C476525:FIS1 protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D020558:GTP Phosphohydrolases; C110768:DNM1L protein, human; D034281:Dynamins; D002118:Calcium