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Originally published as MBC in Press, 10.1091/mbc.E04-09-0807 on November 3, 2004

Vol. 16, Issue 1, 248-259, January 2005

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Formation of Membrane-bound Ring Complexes by Prohibitins in Mitochondria

Takashi Tatsuta *, Kirstin Model {dagger}, and Thomas Langer * {ddagger}

* Institut für Genetik and Zentrum für Molekulare Medizin, Universität zu Köln, 50674 Köln, Germany; {dagger} Max-Planck-Institut für Biophysik, Abteilung für Strukturbiologie, 60439 Frankfurt am Main, Germany

Submitted September 15, 2004; Revised October 21, 2004; Accepted October 26, 2004
Monitoring Editor: Janet Shaw

Prohibitins comprise a remarkably conserved protein family in eukaryotic cells with proposed functions in cell cycle progression, senescence, apoptosis, and the regulation of mitochondrial activities. Two prohibitin homologues, Phb1 and Phb2, assemble into a high molecular weight complex of ~1.2 MDa in the mitochondrial inner membrane, but a nuclear localization of Phb1 and Phb2 also has been reported. Here, we have analyzed the biogenesis and structure of the prohibitin complex in Saccharomyces cerevisiae. Both Phb1 and Phb2 subunits are targeted to mitochondria by unconventional noncleavable targeting sequences at their amino terminal end. Membrane insertion involves binding of newly imported Phb1 to Tim8/13 complexes in the intermembrane space and is mediated by the TIM23-translocase. Assembly occurs via intermediate-sized complexes of ~120 kDa containing both Phb1 and Phb2. Conserved carboxy-terminal coiled-coil regions in both subunits mediate the formation of large assemblies in the inner membrane. Single particle electron microscopy of purified prohibitin complexes identifies diverse ring-shaped structures with outer dimensions of ~270 x 200 Å. Implications of these findings for proposed cellular activities of prohibitins are discussed.


Article published online ahead of print. Mol. Biol. Cell 10.1091/mbc.E04-09-0807. Article and publication date are available at www.molbiolcell.org/cgi/doi/10.1091/mbc.E04-09-0807.

{ddagger} Corresponding author. E-mail address: thomas.langer{at}unikoeln.de.




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