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Molecular and Cellular Biology, May 1999, p. 3842-3847, Vol. 19, No. 5
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Mitochondrial Regulation of Cell Death: Mitochondria Are Essential for Procaspase 3-p21 Complex Formation To Resist Fas-Mediated Cell Death

Atsushi Suzuki,1,2,* Yumi Tsutomi,1 Naoe Yamamoto,3 Tomoko Shibutani,4 and Kouichi Akahane5

Drug Safety Research Laboratory,1 Project for the Cell Death Research,2 New Product Research Laboratory I,3 New Product Research Laboratory II,4 and New Product Research Laboratory IV,5 Daiichi Pharmaceutical Co., Ltd., Edogawa-ku, Tokyo 134-8630, Japan

Received 28 October 1998/Returned for modification 3 January 1999/Accepted 12 February 1999

Death receptor Fas transduces cell death signaling upon stimulation by Fas ligand, and this death signaling is mediated by caspase. Recently, we reported that the cell cycle regulator p21 interacts with procaspase 3 to resist Fas-mediated cell death. In the present study, the molecular characterization and functional region of the procaspase 3-p21 complex was further investigated. We observed the p21 expression in the mitochondrial fraction of HepG2 cells and detected Fas-mediated cell death only in the presence of actinomycin D. However, mitochondrial-DNA-lacking HepG2 (MDLH) cells showed this effect even in the absence of actinomycin D. Both p21 and procaspase 3 were expressed in MDLH cells, but the procaspase 3-p21 complex formation was not observed. Interestingly, the resistance to Fas-mediated cell death in the MDLH cells without actinomycin D was recovered after microinjection of HepG2-derived mitochondria into the MDLH cells. We conclude that mitochondria are necessary for procaspase 3-p21 complex formation and propose that the mitochondrial role during cell death is not only death induction but also death suppression.

* Corresponding author. Mailing address: Drug Safety Research Laboratory, Daiichi Pharmaceutical Co., Ltd., Tokyo R&D Center, Kitakasai 1-16-13, Edogawa-ku, Tokyo 134-8630, Japan. Phone: 81-3-5696-9167. Fax: 81-3-5696-8335. E-mail: LEB00373{at}nifty.ne.jp.

Molecular and Cellular Biology, May 1999, p. 3842-3847, Vol. 19, No. 5
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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