title: Interaction of MDM33 with mitochondrial inner membrane homeostasis pathways in yeast.
abstract: Membrane homeostasis affects mitochondrial dynamics, morphology, and function. Here we report genetic and proteomic data that reveal multiple interactions of Mdm33, a protein essential for normal mitochondrial structure, with components of phospholipid metabolism and mitochondrial inner membrane homeostasis. We screened for suppressors of MDM33 overexpression-induced growth arrest and isolated binding partners by immunoprecipitation of cross-linked cell extracts. These approaches revealed genetic and proteomic interactions of Mdm33 with prohibitins, Phb1 and Phb2, which are key components of mitochondrial inner membrane homeostasis. Lipid profiling by mass spectrometry of mitochondria isolated from Mdm33-overexpressing cells revealed that high levels of Mdm33 affect the levels of phosphatidylethanolamine and cardiolipin, the two key inner membrane phospholipids. Furthermore, we show that cells lacking Mdm33 show strongly decreased mitochondrial fission activity indicating that Mdm33 is critical for mitochondrial membrane dynamics. Our data suggest that MDM33 functionally interacts with components important for inner membrane homeostasis and thereby supports mitochondrial division.
authors.affiliation: Universität Bayreuth, Zellbiologie, 95440 Bayreuth, Germany.
authors.forename: Till
authors.initials: T
authors.lastname: Klecker
authors.affiliation: University of California Davis, Department of Molecular and Cellular Biology, Davis, CA 95616, USA.
authors.forename: Megan
authors.initials: M
authors.lastname: Wemmer
authors.affiliation: Universität zu Köln, Institut für Genetik, 50931 Köln, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Haag
authors.affiliation: Universität Bayreuth, DNA Analytik, 95440 Bayreuth, Germany.
authors.forename: Alfons
authors.initials: A
authors.lastname: Weig
authors.affiliation: Universität Bayreuth, Zellbiologie, 95440 Bayreuth, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Böckler
authors.affiliation: Universität zu Köln, Institut für Genetik, 50931 Köln, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Langer
authors.affiliation: University of California Davis, Department of Molecular and Cellular Biology, Davis, CA 95616, USA.
authors.forename: Jodi
authors.initials: J
authors.lastname: Nunnari
authors.affiliation: Universität Bayreuth, Zellbiologie, 95440 Bayreuth, Germany.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Westermann
mesh_terms: D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D001678:Organelle Biogenesis; D000091402:Prohibitins; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D024101:Mitochondrial Proteins; C000717329:PHB1 protein, S cerevisiae; D000091402:Prohibitins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; C472768:mdm33 protein, S cerevisiae