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
*Corresponding author: Tel,
86-10-62091421; e-mail, [email protected]