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; Joon Oh Young; Myung Shik Lee

doi:10.1038/sj.onc.1205406

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, Joon Oh Young, Myung Shik Lee

Department of Systems Biology

Research output: Contribution to journal › Article › peer-review

9 Citations (Scopus)

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 language	English
Pages (from-to)	3139-3148
Number of pages	10
Journal	Oncogene
Volume	21
Issue number	20
DOIs	https://doi.org/10.1038/sj.onc.1205406
Publication status	Published - 2002

Bibliographical note

Funding Information:
The authors thank Drs K Suk, H-Y Park and P-G Suh for helpful discussion. This work was supported by the National Research Laboratory Grants from the Korea Institute of Science and Technology Evaluation and Planning (2000-N-NL-01-C-232), and Science Research Center Grants from Korea Science and Engineering Foundation. M-S Lee is an awardee of the Juvenile Diabetes Foundation International Research Grant (1-1999-760).

All Science Journal Classification (ASJC) codes

Molecular Biology
Genetics
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/sj.onc.1205406

Cite this

@article{ef640f8474b44876b3db9e6256124b59,

title = "Resistance of mitochondrial DNA-deficient cells to TRAIL: Role of Bax in TRAIL-induced apoptosis",

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.",

author = "Kim, {Ja Young} and Kim, {Yun Hee} and Inik Chang and Sunshin Kim and Youngmi, {Kim Pak} and Oh, {Byung Ha} and Hideo Yagita and Yong, {Keun Jung} and Young, {Joon Oh} and Lee, {Myung Shik}",

note = "Funding Information: The authors thank Drs K Suk, H-Y Park and P-G Suh for helpful discussion. This work was supported by the National Research Laboratory Grants from the Korea Institute of Science and Technology Evaluation and Planning (2000-N-NL-01-C-232), and Science Research Center Grants from Korea Science and Engineering Foundation. M-S Lee is an awardee of the Juvenile Diabetes Foundation International Research Grant (1-1999-760).",

year = "2002",

doi = "10.1038/sj.onc.1205406",

language = "English",

volume = "21",

pages = "3139--3148",

journal = "Oncogene",

issn = "0950-9232",

publisher = "Nature Publishing Group",

number = "20",

}

TY - JOUR

T1 - Resistance of mitochondrial DNA-deficient cells to TRAIL

T2 - Role of Bax in TRAIL-induced apoptosis

AU - Kim, Ja Young

AU - Kim, Yun Hee

AU - Chang, Inik

AU - Kim, Sunshin

AU - Youngmi, Kim Pak

AU - Oh, Byung Ha

AU - Yagita, Hideo

AU - Yong, Keun Jung

AU - Young, Joon Oh

AU - Lee, Myung Shik

N1 - Funding Information: The authors thank Drs K Suk, H-Y Park and P-G Suh for helpful discussion. This work was supported by the National Research Laboratory Grants from the Korea Institute of Science and Technology Evaluation and Planning (2000-N-NL-01-C-232), and Science Research Center Grants from Korea Science and Engineering Foundation. M-S Lee is an awardee of the Juvenile Diabetes Foundation International Research Grant (1-1999-760).

PY - 2002

Y1 - 2002

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85047695600&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85047695600&partnerID=8YFLogxK

U2 - 10.1038/sj.onc.1205406

DO - 10.1038/sj.onc.1205406

M3 - Article

C2 - 12082629

AN - SCOPUS:85047695600

SN - 0950-9232

VL - 21

SP - 3139

EP - 3148

JO - Oncogene

JF - Oncogene

IS - 20

ER -

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

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this