title: Mzm1 influences a labile pool of mitochondrial zinc important for respiratory function.
abstract: Zinc is essential for function of mitochondria as a cofactor for several matrix zinc metalloproteins. We demonstrate that a labile cationic zinc component of low molecular mass exists in the yeast mitochondrial matrix. This zinc pool is homeostatically regulated in response to the cellular zinc status. This pool of zinc is functionally important because matrix targeting of a cytosolic zinc-binding protein reduces the level of labile zinc and interferes with mitochondrial respiratory function. We identified a series of proteins that modulate the matrix zinc pool, one of which is a novel conserved mitochondrial protein designated Mzm1. Mutant mzm1Delta cells have reduced total and labile mitochondrial zinc, and these cells are hypersensitive to perturbations of the labile pool. In addition, mzm1Delta cells have a destabilized cytochrome c reductase (Complex III) without any effects on Complexes IV or V. Thus, we have established that a link exists between Complex III integrity and the labile mitochondrial zinc pool.
authors.affiliation: Department of Medicine and Biochemistry, University of Utah Health Sciences Center, Salt Lake City, Utah 84132, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Atkinson
authors.forename: Oleh
authors.initials: O
authors.lastname: Khalimonchuk
authors.forename: Pamela
authors.initials: P
authors.lastname: Smith
authors.forename: Hana
authors.initials: H
authors.lastname: Sabic
authors.forename: David
authors.initials: D
authors.lastname: Eide
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Winge
mesh_terms: D002176:Candida albicans / Q000378:metabolism*; D002412:Cations; D003579:Cytochrome Reductases / Q000737:chemistry; D004579:Electron Transport; D004591:Electrophoresis, Polyacrylamide Gel; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D005822:Genetic Vectors; D008667:Metalloproteins / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000378:metabolism; D010101:Oxygen Consumption; D010641:Phenotype; D013347:Subcellular Fractions / Q000378:metabolism; D015032:Zinc / Q000737:chemistry
chemical_list: D002412:Cations; D008667:Metalloproteins; D003579:Cytochrome Reductases; D015032:Zinc
references.citation: EMBO J. 2000 Jun 15;19(12):2845-55
references.pmid: 10856230
references.citation: Chem Rev. 2009 Oct;109(10):4708-21
references.pmid: 19522505
references.citation: EMBO J. 2007 Oct 17;26(20):4335-46
references.pmid: 17882260
references.citation: J Biol Chem. 2007 Apr 6;282(14):10423-31
references.pmid: 17234632
references.citation: EMBO J. 1992 Sep;11(9):3219-27
references.pmid: 1324169
references.citation: J Biol Chem. 2006 Aug 25;281(34):24085-9
references.pmid: 16793761
references.citation: J Biol Chem. 1988 Jun 5;263(16):7717-25
references.pmid: 2836393
references.citation: J Biol Chem. 2004 Apr 2;279(14):14447-55
references.pmid: 14729672
references.citation: J Neurosci Methods. 2002 Jul 30;118(1):63-75
references.pmid: 12191759
references.citation: J Biol Chem. 2006 Dec 1;281(48):36552-9
references.pmid: 17008312
references.citation: Biochem Biophys Res Commun. 2002 Aug 30;296(4):923-8
references.pmid: 12200136
references.citation: Cell Calcium. 2003 Sep;34(3):281-4
references.pmid: 12887975
references.citation: Methods Enzymol. 1995;260:117-32
references.pmid: 8592440
references.citation: PLoS One. 2008 May 14;3(5):e2161
references.pmid: 18478128
references.citation: Eukaryot Cell. 2007 Jul;6(7):1166-77
references.pmid: 17526722
references.citation: Nat Chem Biol. 2008 Mar;4(3):168-75
references.pmid: 18277978
references.citation: Genetics. 2002 Oct;162(2):663-76
references.pmid: 12399379
references.citation: Science. 1998 Jul 3;281(5373):64-71
references.pmid: 9651245
references.citation: EMBO Rep. 2008 Nov;9(11):1107-13
references.pmid: 18787558
references.citation: Biochim Biophys Acta. 2006 Jul;1763(7):711-22
references.pmid: 16675045
references.citation: Biochim Biophys Acta. 2000 Aug 15;1459(2-3):440-8
references.pmid: 11004461
references.citation: Proc Natl Acad Sci U S A. 2003 May 13;100(10):6157-62
references.pmid: 12724524
references.citation: Int Rev Neurobiol. 1989;31:145-238
references.pmid: 2689380
references.citation: PLoS Genet. 2009 Mar;5(3):e1000407
references.pmid: 19300474
references.citation: FEMS Yeast Res. 2002 Dec;2(4):481-94
references.pmid: 12702265
references.citation: Methods Cell Biol. 2001;65:37-51
references.pmid: 11381604
references.citation: Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14934-9
references.pmid: 8962159
references.citation: J Biol Chem. 2010 Apr 2;285(14):10408-14
references.pmid: 20075069
references.citation: J Histochem Cytochem. 2008 Jan;56(1):3-6
references.pmid: 17712179
references.citation: J Biol Chem. 2007 Mar 23;282(12):8926-34
references.pmid: 17215247
references.citation: Nat Protoc. 2006;1(1):418-28
references.pmid: 17406264