Endonuclease G is a novel determinant of cardiac hypertrophy and mitochondrial function

Chris McDermott-Roe, Junmei Ye, Rizwan Ahmed, Xi-Ming Sun, Anna Serafín, James Ware, Leonardo Bottolo, Phil Muckett, Xavier Cañas, Jisheng Zhang, Glenn C. Rowe, Rachel Buchan, Han Lu, Adam Braithwaite, Massimiliano Mancini, David Hauton, Ramon Martí, Elena García-Arumí, Norbert Hubner, Howard Jacob, Tadao Serikawa, Vaclav Zidek, Frantisek Papousek, Frantisek Kolar, Maria Cardona, Marisol Ruiz-Meana, David García-Dorado, Joan X. Comella, Leanne E. Felkin, Paul J. R. Barton, Zoltan Arany, Michal Pravenec, Enrico Petretto, Daniel Sanchis () and Stuart A. Cook ()
Additional contact information
Chris McDermott-Roe: Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital
Junmei Ye: Cell Signaling & Apoptosis Group, University Lleida, Biomedical Research Institute of Lleida (IRBLLEIDA), Avenida Rovira Roure 80
Rizwan Ahmed: Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital
Xi-Ming Sun: Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital
Anna Serafín: Platform of Applied Research on Laboratory Animal, Barcelona Science Park, Baldiri Reixac 4
James Ware: Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital
Leonardo Bottolo: Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital
Phil Muckett: Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital
Xavier Cañas: Platform of Applied Research on Laboratory Animal, Barcelona Science Park, Baldiri Reixac 4
Jisheng Zhang: Cell Signaling & Apoptosis Group, University Lleida, Biomedical Research Institute of Lleida (IRBLLEIDA), Avenida Rovira Roure 80
Glenn C. Rowe: Cardiovascular Institute, Beth Israel Deaconess Medical Institute, CLS906, 3 Blackfan Circle
Rachel Buchan: Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital
Han Lu: Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital
Adam Braithwaite: Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital
Massimiliano Mancini: Oncological and Anatomo-Pathological Sciences, University of Rome
David Hauton: School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Edgbaston
Ramon Martí: Unitat de Patologia Mitocondrial i Neuromuscular CIBERER, Institut de Recerca Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona
Elena García-Arumí: Unitat de Patologia Mitocondrial i Neuromuscular CIBERER, Institut de Recerca Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona
Norbert Hubner: Max-Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10
Howard Jacob: Medical College of Wisconsin
Tadao Serikawa: Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University, Yoshidakonoe-cho
Vaclav Zidek: Institute of Physiology, Academy of Sciences of the Czech Republic, Vídenska 1083
Frantisek Papousek: Institute of Physiology, Academy of Sciences of the Czech Republic, Vídenska 1083
Frantisek Kolar: Institute of Physiology, Academy of Sciences of the Czech Republic, Vídenska 1083
Maria Cardona: Cell Signaling & Apoptosis Group, University Lleida, Biomedical Research Institute of Lleida (IRBLLEIDA), Avenida Rovira Roure 80
Marisol Ruiz-Meana: Grup de Patologia Cardiovascular, Institut de Recerca Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Pg. Vall d’Hebron, 119
David García-Dorado: Grup de Patologia Cardiovascular, Institut de Recerca Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Pg. Vall d’Hebron, 119
Joan X. Comella: Cell Signaling & Apoptosis Group at CIBERNED and Vall d’Hebron Institute of Research (VHIR), Pg. Vall d'Hebron, 119-129
Leanne E. Felkin: Heart Science Centre, National Heart and Lung Institute, Imperial College London, Harefield Hospital
Paul J. R. Barton: Heart Science Centre, National Heart and Lung Institute, Imperial College London, Harefield Hospital
Zoltan Arany: Cardiovascular Institute, Beth Israel Deaconess Medical Institute, CLS906, 3 Blackfan Circle
Michal Pravenec: Institute of Physiology, Academy of Sciences of the Czech Republic, Vídenska 1083
Enrico Petretto: Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital
Daniel Sanchis: Cell Signaling & Apoptosis Group, University Lleida, Biomedical Research Institute of Lleida (IRBLLEIDA), Avenida Rovira Roure 80
Stuart A. Cook: Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital

Nature, 2011, vol. 478, issue 7367, 114-118

Abstract: Endonuclease G and heart disease Elevated left ventricular mass, a highly heritable trait, is an important risk factor for heart failure and death. Stuart Cook and colleagues genetically dissect a locus in the rat associated with blood-pressure-independent cardiac hypertrophy and identify endonuclease G (ENDOG) as a key regulator of hypertrophy at this locus. They further show that the Endog gene is involved in proper mitochondrial function and is modulated by ERR-α and PGC1α, master regulators of mitochondrial and cardiac function. Loss of function of ENDOG causes impaired mitochondrial respiration and increased production of reactive oxygen species, which may contribute to the observed cardiac hypertrophy.

Date: 2011
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DOI: 10.1038/nature10490

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