The mitochondrial dicarboxylate and 2-oxoglutarate carriers do not transport glutathione

被引:57
作者
Booty, Lee M. [1 ]
King, Martin S. [1 ]
Thangaratnarajah, Chancievan [1 ]
Majd, Homa [1 ]
James, Andrew M. [1 ]
Kunji, Edmund R. S. [1 ]
Murphy, Michael P. [1 ]
机构
[1] Wellcome Trust Res Labs, Med Res Council Mitochondrial Biol Unit, Cambridge CB2 0XY, England
基金
英国医学研究理事会;
关键词
Mitochondrial carriers; Glutathione transport; Competitive inhibition; Reactive oxygen species; Metabolite exchange; Lactococcus lactis; BACTERIAL EXPRESSION; FUNCTIONAL-CHARACTERIZATION; ADP/ATP CARRIERS; NRK-52E CELLS; IDENTIFICATION; RECONSTITUTION; DEPLETION; OVEREXPRESSION; SACCHAROMYCES; MODULATION;
D O I
10.1016/j.febslet.2015.01.027
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Glutathione carries out vital protective roles within mitochondria, but is synthesised in the cytosol. Previous studies have suggested that the mitochondrial dicarboxylate and 2-oxoglutarate carriers were responsible for glutathione uptake. We set out to characterise the putative glutathione transport by using fused membrane vesicles of Lactococcus lactis overexpressing the dicarboxylate and 2-oxoglutarate carriers. Although transport of the canonical substrates could be measured readily, an excess of glutathione did not compete for substrate uptake nor could transport of glutathione be measured directly. Thus these mitochondrial carriers do not transport glutathione and the identity of the mitochondrial glutathione transporter remains unknown. (C) 2015 The Authors. Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.
引用
收藏
页码:621 / 628
页数:8
相关论文
共 42 条
[31]   Yeast mitochondrial carriers: Bacterial expression, biochemical identification and metabolic significance [J].
Palmieri, L ;
Runswick, MJ ;
Fiermonte, G ;
Walker, JE ;
Palmieri, F .
JOURNAL OF BIOENERGETICS AND BIOMEMBRANES, 2000, 32 (01) :67-77
[32]   Identification by bacterial expression and functional reconstitution of the yeast genomic sequence encoding the mitochondrial dicarboxylate carrier protein [J].
Palmieri, L ;
Palmieri, F ;
Runswick, MJ ;
Walker, JE .
FEBS LETTERS, 1996, 399 (03) :299-302
[33]   Citrin and aralar1 are Ca2+-stimulated aspartate/glutamate transporters in mitochondria [J].
Palmieri, L ;
Pardo, B ;
Lasorsa, FM ;
del Arco, A ;
Kobayashi, K ;
Iijima, M ;
Runswick, MJ ;
Walker, JE ;
Saheki, T ;
Satrústegui, J ;
Palmieri, F .
EMBO JOURNAL, 2001, 20 (18) :5060-5069
[34]   Structure of mitochondrial ADP/ATP carrier in complex with carboxyatractyloside [J].
Pebay-Peyroula, E ;
Dahout-Gonzalez, C ;
Kahn, R ;
Trézéguet, V ;
Lauquin, GJM ;
Brandolin, R .
NATURE, 2003, 426 (6962) :39-44
[35]   An overview on glutathione in Saccharomyces versus non-conventional yeasts [J].
Penninckx, MJ .
FEMS YEAST RESEARCH, 2002, 2 (03) :295-305
[36]   The mechanism of transport by mitochondrial carriers based on analysis of symmetry [J].
Robinson, Alan J. ;
Overy, Catherine ;
Kunji, Edmund R. S. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (46) :17766-17771
[37]   Structures of yeast mitochondrial ADP/ATP carriers support a domain-based alternating-access transport mechanism [J].
Ruprecht, Jonathan J. ;
Hellawell, Alex M. ;
Harding, Marilyn ;
Crichton, Paul G. ;
McCoy, Airlie J. ;
Kunji, Edmund R. S. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2014, 111 (04) :E426-E434
[38]   Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple [J].
Schafer, FQ ;
Buettner, GR .
FREE RADICAL BIOLOGY AND MEDICINE, 2001, 30 (11) :1191-1212
[39]  
Walker J.E., 1992, CURR OPIN STRUC BIOL, V2, P519, DOI [10.1016/0959-440X(92)90081-H, DOI 10.1016/0959-440X(92)90081-H]
[40]   Bcl-2 is a novel interacting partner for the 2-oxoglutarate carrier and a key regulator of mitochondrial glutathione [J].
Wilkins, Heather M. ;
Marquardt, Kristin ;
Lash, Lawrence H. ;
Linseman, Daniel A. .
FREE RADICAL BIOLOGY AND MEDICINE, 2012, 52 (02) :410-419