Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 2745K) PDF+supp data (3302K) PPT slides of all figures Supplemental Material Index Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Osman, C. Articles by Langer, T. Search for Related Content PubMed PubMed Citation Articles by Osman, C. Articles by Langer, T. Related Collections Related Article Social Bookmarking                            What's this?

The genetic interactome of prohibitins: coordinated control of cardiolipin and phosphatidylethanolamine by conserved regulators in mitochondria

¹ Institute for Genetics, Centre for Molecular Medicine (CMMC), Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne 50674, Germany
² Max-Planck-Institute for Biology of Aging, Cologne, Germany
³ Heidelberg University Biochemistry Centre, Heidelberg 69120, Germany
⁴ Institute for Cell Biology and Electron Microscopy Laboratory, University of Bayreuth, Bayreuth 95440, Germany

Correspondence to Thomas Langer: Thomas.Langer{at}uni-koeln.de

Prohibitin ring complexes in the mitochondrial inner membrane regulate cell proliferation as well as the dynamics and function of mitochondria. Although prohibitins are essential in higher eukaryotes, prohibitin-deficient yeast cells are viable and exhibit a reduced replicative life span. Here, we define the genetic interactome of prohibitins in yeast using synthetic genetic arrays, and identify 35 genetic interactors of prohibitins (GEP genes) required for cell survival in the absence of prohibitins. Proteins encoded by these genes include members of a conserved protein family, Ups1 and Gep1, which affect the processing of the dynamin-like GTPase Mgm1 and thereby modulate cristae morphogenesis. We show that Ups1 and Gep1 regulate the levels of cardiolipin and phosphatidylethanolamine in mitochondria in a lipid-specific but coordinated manner. Lipid profiling by mass spectrometry of GEP-deficient mitochondria reveals a critical role of cardiolipin and phosphatidylethanolamine for survival of prohibitin-deficient cells. We propose that prohibitins control inner membrane organization and integrity by acting as protein and lipid scaffolds.

Abbreviations used in this paper: CL, cardiolipin; PE, phosphatidylethanolamine; PS, phosphatidylserine; SGA, synthetic genetic array.

© 2009 Osman et al.
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

CiteULike

Complore

Connotea

Del.icio.us

Digg

Facebook

Reddit

Technorati

Twitter

This article has been cited by other articles:

• Tsubouchi, A., Tsuyama, T., Fujioka, M., Kohda, H., Okamoto-Furuta, K., Aigaki, T., Uemura, T. (2009). Mitochondrial protein Preli-like is required for development of dendritic arbors and prevents their regression in the Drosophila sensory nervous system. Development 136: 3757-3766 [Abstract] [Full Text]  
• Osman, C., Merkwirth, C., Langer, T. (2009). Prohibitins and the functional compartmentalization of mitochondrial membranes. J. Cell Sci. 122: 3823-3830 [Abstract] [Full Text]  
• Rijken, P. J., Houtkooper, R. H., Akbari, H., Brouwers, J. F., Koorengevel, M. C., de Kruijff, B., Frentzen, M., Vaz, F. M., de Kroon, A. I. P. M. (2009). Cardiolipin Molecular Species with Shorter Acyl Chains Accumulate in Saccharomyces cerevisiae Mutants Lacking the Acyl Coenzyme A-binding Protein Acb1p: NEW INSIGHTS INTO ACYL CHAIN REMODELING OF CARDIOLIPIN. J. Biol. Chem. 284: 27609-27619 [Abstract] [Full Text]  
• Tatsuta, T. (2009). Protein Quality Control in Mitochondria. J Biochem 146: 455-461 [Abstract] [Full Text]  
• Wiedemann, N., Meisinger, C., Pfanner, N. (2009). Connecting Organelles. Science 325: 403-404 [Abstract] [Full Text]  
• Kornmann, B., Currie, E., Collins, S. R., Schuldiner, M., Nunnari, J., Weissman, J. S., Walter, P. (2009). An ER-Mitochondria Tethering Complex Revealed by a Synthetic Biology Screen. Science 325: 477-481 [Abstract] [Full Text]  
• Tamura, Y., Endo, T., Iijima, M., Sesaki, H. (2009). Ups1p and Ups2p antagonistically regulate cardiolipin metabolism in mitochondria. JCB 185: 1029-1045 [Abstract] [Full Text]  
• Gohil, V. M., Greenberg, M. L. (2009). Mitochondrial membrane biogenesis: phospholipids and proteins go hand in hand. JCB 184: 469-472 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents