Resistance of mitochondrial DNA-deficient cells to TRAIL: Role of Bax in TRAIL-induced apoptosis

Ja Young Kim, Yun Hee Kim, Inik Chang, Sunshin Kim, Kim Pak Youngmi, Byung Ha Oh, Hideo Yagita, Keun Jung Yong, Young Jun Oh, Myung Shik Lee

Research output: Contribution to journalArticle

Abstract

Mitochondrion is one of the master players in both apoptosis and necrosis. We studied the role of mitochondrial function in TRAIL-induced apoptosis. TRAIL killed SK-Hep1 cells with characteristic features of apoptosis such as DNA fragmentation, sub-G1 ploidy peak and cytochrome c translocation. In contrast, mitochondrial DNA-deficient SK-Hep1 ρ0 cells were resistant to TRAIL. Dissipation of mitochondrial potential or cytochrome c translocation did not occur in ρ0 cells after TRAIL treatment. TRAIL induced translocation of Bax subsequent to the cleavage of Bid in parental cells. However, Bax translocation was absent in ρ0 cells, accounting for the failure of cytochrome c release in ρ0 cells. Forced expression of Bax induced caspase-3 activity in ρ0 cells. Incubation of ρ0 cells with ADP+Pi to increase intracellular ATP restored sensitivity to TRAIL. Despite different sensitivity to TRAIL, parental cells and ρ0 cells did not show significant difference in susceptibility to agonistic antiFas antibody, TNF-α or staurosporine. Our results indicate that TRAIL-induced apoptosis is dependent on intact mitochondrial function and susceptibility of mitochondrial DNA-deficient cells to apoptosis depends on the type of apoptotic stimuli. Tumor cells with mitochondrial mutations or dysfunction might have the ability to evade tumor surveillance imposed by TRAIL in vivo.

Original languageEnglish
Pages (from-to)3139-3148
Number of pages10
JournalOncogene
Volume21
Issue number20
DOIs
Publication statusPublished - 2002 May 9

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All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Kim, J. Y., Kim, Y. H., Chang, I., Kim, S., Youngmi, K. P., Oh, B. H., Yagita, H., Yong, K. J., Oh, Y. J., & Lee, M. S. (2002). Resistance of mitochondrial DNA-deficient cells to TRAIL: Role of Bax in TRAIL-induced apoptosis. Oncogene, 21(20), 3139-3148. https://doi.org/10.1038/sj/onc/1205406