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

J. Biol. Chem., Vol. 278, Issue 34, 32091-32099, August 22, 2003

This Article Full Text Full Text (PDF) An addition or correction has been published All Versions of this Article: 278/34/32091    most recent M304877200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sanz, M. A. Articles by Nijtmans, L. G. J. Search for Related Content PubMed PubMed Citation Articles by Sanz, M. A. Articles by Nijtmans, L. G. J. Social Bookmarking                      What's this?

The Mitochondrial Prohibitin Complex Is Essential for Embryonic Viability and Germline Function in Caenorhabditis elegans^*

Marta Artal Sanz  , William Y. Tsang ¶, Esther M. Willems , Les A. Grivell  ||, Bernard D. Lemire ¶, Hans van der Spek  ** and Leo G. J. Nijtmans ** 

From the Swammerdam Institute for Life Sciences, Section for Molecular Biology, University of Amsterdam, Kruislaan 318, Amsterdam 1098 SM, The Netherlands, ^¶Canadian Institutes of Health Research, Membrane Protein Research Group, Department of Biochemistry, University of Alberta, Edmonton T6G 2H7, Canada, and Nijmegen Center for Mitochondrial Disorders, University Medical Center Nijmegen, Geert Grooteplein 10, Nijmegen 6500 HB, The Netherlands

Prohibitins in eukaryotes consist of two subunits (PHB1 and PHB2) that together form a high molecular weight complex in the mitochondrial inner membrane. The evolutionary conservation and the ubiquitous expression in mammalian tissues of the prohibitin complex suggest an important function among eukaryotes. The PHB complex has been shown to play a role in the stabilization of newly synthesized subunits of mitochondrial respiratory enzymes in the yeast Saccharomyces cerevisiae. We have used Caenorhabditis elegans as model system to study the role of the PHB complex during development of a multicellular organism. We demonstrate that prohibitins in C. elegans form a high molecular weight complex in the mitochondrial inner membrane similar to that of yeast and humans. By using RNA-mediated gene inactivation, we show that PHB proteins are essential during embryonic development and are required for somatic and germline differentiation in the larval gonad. We further demonstrate that a deficiency in PHB proteins results in altered mitochondrial biogenesis in body wall muscle cells. This paper reports a strong loss of function phenotype for prohibitin gene inactivation in a multicellular organism and shows for the first time that prohibitins serve an essential role in mitochondrial function during organismal development.

Received for publication, May 9, 2003 , and in revised form, June 5, 2003.

^* This work was supported by European Commission Grant QLG1-CT-2001-00966. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^|| Present address: EMBO, Meyerhofstrasse I, D-69117 Heidelberg, Germany.

^** These two authors contributed equally to this work.

To whom correspondence should be addressed. Tel.: 31-20-5257921; Fax: 31-20-5257924; E-mail: artal{at}science.uva.nl.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				I. Bratic, J. Hench, J. Henriksson, A. Antebi, T. R Burglin, and A. Trifunovic Mitochondrial DNA level, but not active replicase, is essential for Caenorhabditis elegans development Nucleic Acids Res., April 1, 2009; 37(6): 1817 - 1828. [Abstract] [Full Text] [PDF]

				C. Osman, M. Haag, C. Potting, J. Rodenfels, P. V. Dip, F. T. Wieland, B. Brugger, B. Westermann, and T. Langer The genetic interactome of prohibitins: coordinated control of cardiolipin and phosphatidylethanolamine by conserved regulators in mitochondria J. Cell Biol., February 23, 2009; 184(4): 583 - 596. [Abstract] [Full Text] [PDF]

				J. A. Ross, Z. S. Nagy, and R. A. Kirken The PHB1/2 Phosphocomplex Is Required for Mitochondrial Homeostasis and Survival of Human T Cells J. Biol. Chem., February 22, 2008; 283(8): 4699 - 4713. [Abstract] [Full Text] [PDF]

				C. Merkwirth, S. Dargazanli, T. Tatsuta, S. Geimer, B. Lower, F. T. Wunderlich, J.-C. von Kleist-Retzow, A. Waisman, B. Westermann, and T. Langer Prohibitins control cell proliferation and apoptosis by regulating OPA1-dependent cristae morphogenesis in mitochondria Genes & Dev., February 15, 2008; 22(4): 476 - 488. [Abstract] [Full Text] [PDF]

				M. Schleicher, B. R. Shepherd, Y. Suarez, C. Fernandez-Hernando, J. Yu, Y. Pan, L. M. Acevedo, G. S. Shadel, and W. C. Sessa Prohibitin-1 maintains the angiogenic capacity of endothelial cells by regulating mitochondrial function and senescence J. Cell Biol., January 10, 2008; 180(1): 101 - 112. [Abstract] [Full Text] [PDF]

				I. Marques, N. A. Dencher, A. Videira, and F. Krause Supramolecular Organization of the Respiratory Chain in Neurospora crassa Mitochondria Eukaryot. Cell, December 1, 2007; 6(12): 2391 - 2405. [Abstract] [Full Text] [PDF]

				P. Hajek, A. Chomyn, and G. Attardi Identification of a Novel Mitochondrial Complex Containing Mitofusin 2 and Stomatin-like Protein 2 J. Biol. Chem., February 23, 2007; 282(8): 5670 - 5681. [Abstract] [Full Text] [PDF]

				I. Chowdhury, W. Xu, J. K. Stiles, A. Zeleznik, X. Yao, R. Matthews, K. Thomas, and W. E. Thompson Apoptosis of Rat Granulosa Cells after Staurosporine and Serum Withdrawal Is Suppressed by Adenovirus-Directed Overexpression of Prohibitin Endocrinology, January 1, 2007; 148(1): 206 - 217. [Abstract] [Full Text] [PDF]

				A. L. Theiss, R. D. Idell, S. Srinivasan, J.-M. Klapproth, D. P. Jones, D. Merlin, and S. V. Sitaraman Prohibitin protects against oxidative stress in intestinal epithelial cells FASEB J, January 1, 2007; 21(1): 197 - 206. [Abstract] [Full Text] [PDF]

				K. Kasashima, E. Ohta, Y. Kagawa, and H. Endo Mitochondrial Functions and Estrogen Receptor-dependent Nuclear Translocation of Pleiotropic Human Prohibitin 2 J. Biol. Chem., November 24, 2006; 281(47): 36401 - 36410. [Abstract] [Full Text] [PDF]

				I. Zubovych, T. Doundoulakis, P. G. Harran, and M. G. Roth A missense mutation in Caenorhabditis elegans prohibitin 2 confers an atypical multidrug resistance PNAS, October 17, 2006; 103(42): 15523 - 15528. [Abstract] [Full Text] [PDF]

				C. Benedetti, C. M. Haynes, Y. Yang, H. P. Harding, and D. Ron Ubiquitin-Like Protein 5 Positively Regulates Chaperone Gene Expression in the Mitochondrial Unfolded Protein Response Genetics, September 1, 2006; 174(1): 229 - 239. [Abstract] [Full Text] [PDF]

				H. Nomura, S. B. P. Athauda, H. Wada, Y. Maruyama, K. Takahashi, and H. Inoue Identification and Reverse Genetic Analysis of Mitochondrial Processing Peptidase and the Core Protein of the Cytochrome bc1 Complex of Caenorhabditis elegans, a Model Parasitic Nematode J. Biochem., June 1, 2006; 139(6): 967 - 979. [Abstract] [Full Text] [PDF]

				T. Tatsuta, K. Model, and T. Langer Formation of Membrane-bound Ring Complexes by Prohibitins in Mitochondria Mol. Biol. Cell, January 1, 2005; 16(1): 248 - 259. [Abstract] [Full Text] [PDF]

				S. P. Curran, E. P. Leverich, C. M. Koehler, and P. L. Larsen Defective Mitochondrial Protein Translocation Precludes Normal Caenorhabditis elegans Development J. Biol. Chem., December 24, 2004; 279(52): 54655 - 54662. [Abstract] [Full Text] [PDF]

				T. Yoneda, C. Benedetti, F. Urano, S. G. Clark, H. P. Harding, and D. Ron Compartment-specific perturbation of protein handling activates genes encoding mitochondrial chaperones J. Cell Sci., August 15, 2004; 117(18): 4055 - 4066. [Abstract] [Full Text] [PDF]

				T. Jonassen, D. E. Davis, P. L. Larsen, and C. F. Clarke Reproductive Fitness and Quinone Content of Caenorhabditis elegans clk-1 Mutants Fed Coenzyme Q Isoforms of Varying Length J. Biol. Chem., December 19, 2003; 278(51): 51735 - 51742. [Abstract] [Full Text] [PDF]