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Resistance of ρ 0 Cells against Apoptosis
Author(s) -
LEE MYUNGSHIK,
KIM JAYOUNG,
PARK SUN YOUNG
Publication year - 2004
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1293.015
Subject(s) - apoptosis , cytochrome c , mitochondrion , biology , dna fragmentation , mitochondrial apoptosis induced channel , mitochondrial dna , staurosporine , effector , microbiology and biotechnology , programmed cell death , cancer cell , fragmentation (computing) , cancer , genetics , phosphorylation , gene , protein kinase c , ecology
A bstract : Mitochondrion is one of the master players in both apoptosis and necrosis. However, most previous articles report that mitochondrial DNA‐depleted cells without oxidative phosphorylation underwent apoptosis by several apoptotic effectors as efficiently as their parental cells, suggesting that intact mitochondrial function is dispensable for the progression of apoptosis. We studied the role of mitochondrial function in several apoptosis models. TRAIL, a recently identified member of the TNF family with cytotoxicity on a wide variety of transformed cells, killed SK‐Hep1 cells with characteristic features of apoptosis such as DNA fragmentation, sub‐G1 ploidy peak, and cytochrome c translocation. In contrast with parental cells, mitochondrial DNA‐deficient SK‐Hep1 ρ 0 cells were resistant to TRAIL‐induced apoptosis. Dissipation of mitochondrial potential or cytochrome c translocation did not occur in ρ 0 cells after TRAIL treatment. Bax translocation also was absent in ρ 0 cells, accounting for the failure of cytochrome c release in ρ 0 cells. SK‐Hep1 ρ 0 cells were resistant to other death effectors such as staurosporine. Our results indicate that apoptosis of SK‐Hep1 hepatoma cells is dependent on intact mitochondrial function. Because aged cells or tumor cells have frequent mutations or deletions of mitochondrial DNA, they might acquire the ability to evade apoptosis or tumor surveillance imposed by TRAIL or other death effectors in vivo , accounting for the selection advantage of cancer cells and frequent development of cancer in aged individuals.