HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: fj.06-6283comv1 21/1/188    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kim, H.-R. Articles by Reed, J. C. Search for Related Content PubMed PubMed Citation Articles by Kim, H.-R. Articles by Reed, J. C.

Mammalian dap3 is an essential gene required for mitochondrial homeostasis in vivo and contributing to the extrinsic pathway for apoptosis

Burnham Institute for Medical Research, La Jolla, California, USA

⁵Correspondence: Burnham Institute for Medical Research, 10901 N. Torrey Pines Road, La Jolla, CA 92037, USA. E-mail: reedoffice{at}burnham.org

Death-associated protein-3 (DAP3) is a GTP binding protein previously implicated in both intramitochondrial protein synthesis and apoptosis. To explore the in vivo roles of DAP3, we generated and characterized DAP3-deficient mice. Homozygous dap3^–/– embryos died at day 9.5 in utero. The dap3^–/– embryos and placentas were markedly shrunken. Embryos had arrested development, displaying severe growth restriction and lack of axial turning. Transmission electron microscopy analysis revealed abnormal, shrunken mitochondria with swollen crystae in dap3^–/– embryos. Levels of cytochrome c oxidase-I, a protein encoded in the mitochondrial genome, were reduced in dap3^–/– embryos, consistent with a role for DAP3 in intramitochondrial protein synthesis. A requirement for DAP3 in mitochondrial respiration was also revealed by oxygen consumption measurements using cultured cells treated with DAP3-specific small interfering RNA (siRNA). Studies of cultured cells from dap3^–/– embryos confirmed a role in apoptosis induced by stimuli that trigger the extrinsic (TNF, TRAIL, anti-Fas antibody) but not intrinsic (mitochondrial) cell death pathway. Thus, DAP3 joins a growing list of bifunctional proteins that play roles in normal mitochondrial physiology and in apoptosis.—Kim, H-R, Chae, H-J., Thomas, M., Miyazaki, T., Monosov, A., Monosov, E., Krajewska, M., Krajewski, S., Reed, J. C. Mammalian dap3 is an essential gene required for mitochondrial homeostasis in vivo and contributing to the extrinsic pathway for apoptosis.

Key Words: mitochondrial respiration • DAP3 protein • genotypic analysis • ß-actin • GTP binding protein

This article has been cited by other articles:

				T. Tang, B. Zheng, S.-h. Chen, A. N. Murphy, K. Kudlicka, H. Zhou, and M. G. Farquhar hNOA1 Interacts with Complex I and DAP3 and Regulates Mitochondrial Respiration and Apoptosis J. Biol. Chem., February 20, 2009; 284(8): 5414 - 5424. [Abstract] [Full Text] [PDF]