Mutational Analysis of the QRRQ Motif in the Yeast Hig1 Type 2 Protein Rcf1 Reveals a Regulatory Role for the Cytochrome c Oxidase Complex

被引:30
作者
Garlich, Joshua [1 ]
Strecker, Valentina [2 ]
Wittig, Ilka [2 ]
Stuart, Rosemary A. [1 ]
机构
[1] Marquette Univ, Dept Biol Sci, 530 N 15th St, Milwaukee, WI 53233 USA
[2] Goethe Univ, Funct Prote, SFB Core Unit 815, D-60590 Frankfurt, Germany
基金
美国国家科学基金会; 美国国家卫生研究院;
关键词
RESPIRATORY-CHAIN; OXIDATIVE-PHOSPHORYLATION; SUPERCOMPLEX ORGANIZATION; MITOCHONDRIAL PROTEIN; CARDIOLIPIN; IDENTIFICATION; COMPONENTS; INSIGHT; GLUCOSE; HIGD1A;
D O I
10.1074/jbc.M116.758045
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
The yeast Rcf1 protein is a member of the conserved family of proteins termed the hypoxia-induced gene (domain) 1 (Hig1 or HIGD1) family. Rcf1 interacts with components of the mitochondrial oxidative phosphorylation system, in particular the cytochrome bc(1) (complex III)-cytochrome c oxidase (complex IV) supercomplex (termed III-IV) and the ADP/ATP carrier proteins. Rcf1 plays a role in the assembly and modulation of the activity of complex IV; however, the molecular basis for how Rcf1 influences the activity of complex IV is currently unknown. Hig1 type 2 isoforms, which include the Rcf1 protein, are characterized in part by the presence of a conserved motif, (Q/I) X-3(R/H) XRX(3)Q, termed here the QRRQ motif. We show that mutation of conserved residues within the Rcf1 QRRQ motif alters the interactions between Rcf1 and partner proteins and results in the destabilization of complex IV and alteration of its enzymatic properties. Our findings indicate that Rcf1 does not serve as a stoichiometric component, i.e. as a subunit of complex IV, to support its activity. Rather, we propose that Rcf1 serves to dynamically interact with complex IV during its assembly process and, in doing so, regulates a late maturation step of complex IV. We speculate that the Rcf1/Hig1 proteins play a role in the incorporation and/or remodeling of lipids, in particular cardiolipin, into complex IV and. possibly, other mitochondrial proteins such as ADP/ATP carrier proteins.
引用
收藏
页码:5216 / 5226
页数:11
相关论文
共 41 条
  • [1] HIGD1A Regulates Oxygen Consumption, ROS Production, and AMPK Activity during Glucose Deprivation to Modulate Cell Survival and Tumor Growth
    Ameri, Kurosh
    Jahangiri, Arman
    Rajah, Anthony M.
    Tormos, Kathryn V.
    Nagarajan, Ravi
    Pekmezci, Melike
    Vien Nguyen
    Wheeler, Matthew L.
    Murphy, Michael P.
    Sanders, Timothy A.
    Jeffrey, Stefanie S.
    Yeghiazarians, Yerem
    Rinaudo, Paolo F.
    Costello, Joseph F.
    Aghi, Manish K.
    Maltepe, Emin
    [J]. CELL REPORTS, 2015, 10 (06): : 891 - 899
  • [2] Nuclear Localization of the Mitochondrial Factor HIGD1A during Metabolic Stress
    Ameri, Kurosh
    Rajah, Anthony M.
    Vien Nguyen
    Sanders, Timothy A.
    Jahangiri, Arman
    DeLay, Michael
    Donne, Matthew
    Choi, Hwa J.
    Tormos, Kathryn V.
    Yeghiazarians, Yerem
    Jeffrey, Stefanie S.
    Rinaudo, Paolo F.
    Rowitch, David H.
    Aghi, Manish
    Maltepe, Emin
    [J]. PLOS ONE, 2013, 8 (04):
  • [3] BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3
  • [4] Sallp, a calcium-dependent cartier protein that suppresses an essential cellular function associated with the Aac2 isoform of ADP/ATP translocase in Saccharomyces cerevisiae
    Chen, XJ
    [J]. GENETICS, 2004, 167 (02) : 607 - 617
  • [5] Identification of a Protein Mediating Respiratory Supercomplex Stability
    Chen, Yu-Chan
    Taylor, Eric B.
    Dephoure, Noah
    Heo, Jin-Mi
    Tonhato, Aline
    Papandreou, Ioanna
    Nath, Nandita
    Denko, Nicolas C.
    Gygi, Steven P.
    Rutter, Jared
    [J]. CELL METABOLISM, 2012, 15 (03) : 348 - 360
  • [6] Cardiolipin defines the interactome of the major ADP/ATP carrier protein of the mitochondrial inner membrane
    Claypool, Steven M.
    Oktay, Yavuz
    Boontheung, Pinmanee
    Loo, Joseph A.
    Koehler, Carla M.
    [J]. JOURNAL OF CELL BIOLOGY, 2008, 182 (05) : 937 - 950
  • [7] The Cardiolipin Transacylase, Tafazzin, Associates with Two Distinct Respiratory Components Providing Insight into Barth Syndrome (vol 19, pg 5143, 2008)
    Claypool, Steven M.
    [J]. MOLECULAR BIOLOGY OF THE CELL, 2012, 23 (13) : 2619 - 2619
  • [8] MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification
    Cox, Juergen
    Mann, Matthias
    [J]. NATURE BIOTECHNOLOGY, 2008, 26 (12) : 1367 - 1372
  • [9] The cytochrome bc1 and cytochrome c oxidase complexes associate to form a single supracomplex in yeast mitochondria
    Cruciat, CM
    Brunner, S
    Baumann, F
    Neupert, W
    Stuart, RA
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (24) : 18093 - 18098
  • [10] The Yeast Aac2 Protein Exists in Physical Association with the Cytochrome bc1-COX Supercomplex and the TIM23 Machinery (vol 19, pg 3934, 2008)
    Marques, I
    Dencher, N. A.
    Videira, A.
    Krause, F.
    [J]. MOLECULAR BIOLOGY OF THE CELL, 2009, 20 (03) : 1118 - 1118