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Abstract #3518

Mitochondrial Skeletal Muscle Uncoupling in a Murine Cancer Cachexia Model

Valeria Righi1, 2, Cibely Cristine Fontes De Oliveira3, Alexander A. Shestov4, Dionyssios Mintzopoulos1, 5, Nikolaos Psychogios1, 5, Caterina Constantinou1, 6, Silvia Busquets3, Francisco J. Lopez-Soriano3, Sylvain Milot7, Francois Lepine8, Michael N. Mindrinos9, Laurence G. Rahme6, Josep M. Argiles3, Aria A. Tzika1, 5

1NMR Surgical Laboratory, Department of Surgery, Massachusetts General Hospital and Shriners Burn Institute, Harvard Medical School, Boston, MA, United States; 2Department of Science for Life Quality, University of Bologna, Rimini, Italy; 3Cancer Research Group, Department de Bioqumica y Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain; 4Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota Medical School, Minneapolis, MN, United States; 5Department of Radiology, Athinoula A. Martinos Center of Biomedical Imaging, Boston, MA, United States; 6Molecular Surgery Laboratory, Department of Surgery, Massachusetts General Hospital and Shriners Burn Institute, Harvard Medical School, Boston, MA, United States; 7INRS-Institut Armand-Frappier, Universit du Qubec, Laval,, Quebec, Canada; 8INRS-Institut Armand-Frappier, Universit du Qubec, Leval, Quebec, Canada; 9Department of Biochemistry, Stanford University School of Medicine, Stanford,, CA, United States

We tested the hypothesis that cancer promotes mitochondrial uncoupling in skeletal muscle. We employed in vivo 31P NMR on intact mice and GC-MS in skeletal muscle samples, in a mouse cancer cachexia model. ATP synthesis rate and TCA cycle flux were significantly reduced in cancer-bearing mice. The ratio of ATP synthesis rate/TCA cycle flux, which provides an index of mitochondrial coupling, was 32% less in cancer-bearing mice. Our results were cross-validated with genomic analysis, showing aberrant expression levels in key regulatory genes and by electron microscopy showing abnormal giant mitochondria.

Keywords

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