TFAR19 Enhances the Opening of Permeability Transition Pore in the Mitochondrial Membrane of Mice Liver

TIAN Hui-Kai, XIA Tian¹, JIANG Chun-Sun², ZHANG Hong-Mei, WANG Kun³, LI Xue-Jun^*
( Department of Pharmacology,Peking University Health Science Center,Beijing 100083,China;¹National Key Lab of Biomembrane and Membrane Biotechnology,Peking University,Beijing 100871,China; ²Tianjin Sports Institute,Tianjin 300381,China; ³General Surgery,the Third Affiliated Hospital of Peking University,Beijing 100083,China )

Abstract TFAR19（TF-1 cell apoptosis related gene 19）is a novel apoptosis-related gene cloned from human leukemia cell line TF-1 cells undergoing apoptosis in 1999 (accession number AF014955 in GenBank).The human TFAR19 encodes a protein which shares significant homology to the corresponding proteins of species ranging from yeast to mice. TFAR19 exhibits a ubiquitous expression pattern and its expression is upregulated in tumor cells undergoing apoptosis. Overexpression of TFAR19 could enhance apoptosis of some tumor cells induced by growth factor withdrawal or serum deprivation. But the exact mechanism of TFAR19 is unclear. Mitochondria not only provides energy for the cell, but also plays a critical role on cell death or survival. The release of apoptosis promoting factor, such as cytochrome c from mitochondria, resulted by the damage of mitochondrial membraneintegrity, is the key factor controlling apoptosis. The permeability transition pore (PTP) of mitochondria is a protein complex located between the mitochondrial membranes, and it plays an important role in regulating the integrity of mitochondrial membrane. In this study, the effect of recombinant TFAR19 on isolated mitochondrial PTP, membrane potential, and release of cytochrome c was investigated in vitro. The results indicated that recombinant TFAR19 facilitated the isolated mitochondrial PTP opening, decreased the membrane potential, and promoted the release of cytochrome c. The effect of TFAR19 on mitochondria is implemented by opening the mitochondrial PTP. Experimental results implicate that TFAR19 maypositively feedback apoptosis signal of mitochondria, forming a positive loop to promote apoptosis.
Key words    apoptosis; TFAR19; mitochondria; PTP; membrane potential

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