FUNCTIONAL GENETICS OF THE OXIDATIVE PHOSPHORILATION SYSTEM

Group Members 

Acisclo Pérez-Martos	Associated Professor
Patricio Fernández-Silva	Associated Professor
José Antonio Enríquez	Full Professor (Coordinator)
Pilar Bayona-Bafaluy	Post-doctoral "Ramon y Cajal"
Patricia Meade Huerta	Post-doctoral Consolider
Nuria Garrido Pérez	Asistant Professor PhD
Erika Fernádez-Vizarra	Post-doctoral "Juan de la Cierva"
Raquel Moreno Loshuertos	PhD fellow Asistant Professor
Ester Perales Clemente	PhD fellow
Ricardo Marco Lázaro	PhD fellow
Elena de Tomas Mateo	PhD fellow
Ana Latorre Pellicer	PhD fellow
Esther Lapuente Bru	PhD fellow
Nieves Movilla Meno	Lab Manager

Visitors

Former Group Members

Rebeca Acín-Pérez, PhD

  Gustavo Ferrin Sánchez, PhD

Contact

Departamento de BioquÃmica y BiologÃa Molecular y Celular.
Universidad de Zaragoza.
C/ Miguel Servet, 177.
50013 Zaragoza. SPAIN

Genoxphos Group

Research Lines

Our research is centered in basic issues about the functional regulation of the OXPHOS system, its biogenesis and its structural organization. In addition, we are pursuing the molecular understanding of the diseases caused by its dysfunction and investigating potential therapies. Therefore we are able to design functional genetic studies of the OXPHOS system involving genes encoded by the mtDNA and by the nDNA. The primary objectives that we are facing are: Funtional genetics of animal mtDNA. We are generating a systematic collection of mouse cells with single point mutations at its mtDNA that impair OXPHOS. Mammalian mtDNA coded for 37 genes (13 structural porteins, 22 tRNAs and 2 rRNAs). Seven proteins are structural subunits of Complex I, one of Complex III, three of Complex IV and two of Complex V. We already have cells harboring single point mutations affecting eight mtDNA genes. Animal Models of mtDNA diseases. We are generating mice harboring mutant mtDNA. Functional consequences of allelic variants of the mtDNA. We are also establishing human and mouse cell lines harboring different common haplotypes of mtDNA with the purpose of study the implications of natural mtDNA polymorphisms in humans and mice as genetic factors influencing pathology and/or different phenotypes as fertility, ROS signaling, etc. In the case of mice we have identify five allelic mtDNA variants in common laboratory strains that can be associated with deafness susceptibility, intelligence and other phenotypes. These associations lack any molecular explanation. In our cellular models we have identify a potential molecular cause for this associations that involve ROS handling . Nuclear genes involved in OXPHOS: We are applying high-throughput approaches in cell culture to identify and characterize non-essential genes required for the proper biogenesis and performance of the OXPHOS system.

Recent Publications

Recent Mitochondrial Publications

(1) Bayona-Bafaluy MP, Movilla N, Perez-Martos A, Fernandez-Silva P, Enriquez JA. Functional genetic analysis of the mammalian mitochondrial DNA encoded peptides: a mutagenesis approach. Methods Mol Biol. 2008;457:379-90.

(2) Acin-Perez R, Fernandez-Silva P, Peleato ML, Perez-Martos A, Enriquez JA. Respiratory active mitochondrial supercomplexes.  Mol Cell. 2008 Nov 21;32(4):529-39.

(3) Perales-Clemente E, Bayona-Bafaluy MP, Perez-Martos A, Barrientos A, Fernandez-Silva P, Enriquez JA.  Restoration of electron transport without proton pumping in mammalian mitochondria. Proc Natl Acad Sci U S A. 2008 Dec 2;105(48):18735-9.

(4) Fernandez-Vizarra E, Enriquez JA, Perez-Martos A, Montoya J, Fernandez-Silva P. Mitochondrial gene expression is regulated at multiple levels and differentially in the heart and liver by thyroid hormones. Curr Genet. 2008 Jul;54(1):13-22. Epub 2008 May 15.

(5)  Garrido N, Perez-Martos A, Faro M, Lou-Bonafonte JM, Fernandez-Silva P, Lopez-Perez MJ, Montoya J, Enriquez JA. Cisplatin-mediated impairment of mitochondrial DNA metabolism inversely correlates with glutathione levels. Biochem J. 2008 Aug 15;414(1):93-102.

(6) Fernandez-Silva P, Acin-Perez R, Ferandez-Vizarra E, Perez-Martos A, Enriquez JA. In vivo and in organello analyses of mitochondrial translation. Methods Cell Biol. 2007;80:571-88.

(7) Ruiz-Pesini E, Diez-Sanchez C, Lopez-Perez MJ, Eniquez JA. The role of the mitochondrion in sperm function: is there a place for oxidative phosphorylation or is this a purely glycolytic process? Curr Top Dev Biol. 2007;77:3-19.

(8) Moreno-Loshuertos R, Acin-Perez R, Fernandez-Silva P, Movilla N, Perez-Martos A, de Cordoba SR, Gallardo ME, Enriquez JA. Differences in reactive oxygen species production explain the phenotypes associated with common mouse mitochondrial DNA variants. Nat Genet. 2006 Nov;38(11):1261-8.

(9) Gallardo ME, Moreno-Loshuertos R, Lopez C, Casqueiro M, Silva J, Bonilla F, Rodriguez de Cordoba S, Enriquez JA. m.6267G>A: a recurrent mutation in the human mitochondrial DNA that reduces cytochrome c oxidase activity and is associated with tumors. Hum Mutat. 2006 Jun;27(6):575-82.

(10) Acin-Perez R, Bayona-Bafaluy MP, Fernandez-Silva P, Moreno-Loshuertos R, Perez-Martos A, Bruno C, Moraes CT, Enriquez JA. Respiratory complex III is required to maintain complex I in mammalian mitochondria. Mol Cell. 2004 Mar 26;13(6):805-15

(11) Bayona-Bafaluy MP, Acin-Perez R, Mullikin JC, Park JS, Moreno-Loshuertos R, Hu P, Perez-Martos A, Fernandez-Silva P, Bai Y, Enriquez JA. Revisiting the mouse mitochondrial DNA sequence. Nucleic Acids Res. 2003 Sep 15;31(18):5349-55.

(12) Acin-Perez R, Bayona-Bafaluy MP, Bueno M, Machicado C, Fernandez-Silva P, Perez-Martos A, Montoya J, Lopez-Perez MJ, Sancho J, Enriquez JA. An intragenic suppressor in the cytochrome c oxidase I gene of mouse mitochondrial DNA. Hum Mol Genet. 2003 Feb 1;12(3):329-39.

Additional publications

Support

	Grupo de  excelencia B55

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