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The Relevance of the Mitochondrial H+-ATP Synthase in Cancer Biology

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Tumor Cell Metabolism

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Abstract

Cancer cells depend on metabolic changes to cover the increased energy and metabolite demands that sustain proliferation. The enhanced rate of aerobic glycolysis and the activation of other metabolic pathways provide the energy and building blocks that support cell division. These changes occurred in response to the partial silencing of the bioenergetic function of mitochondria, specifically of the H+-ATP synthase, which is the engine that produces most of the ATP that sustains cellular activities in normal differentiated aerobic cells. Changes in the bioenergetic phenotype of carcinomas can be assessed by the determination of the expression of the catalytic subunit of the H+-ATP synthase (β-F1-ATPase) relative to the expression of the enzyme of glycolysis glyceraldehyde-3-phosphate dehydrogenase (GAPDH). The β-F1-ATPase/GAPDH ratio provides a bioenergetic signature of the tumor with clinical relevance as a molecular marker of the prognosis of different cancer patients as well as of the tumor response to chemotherapy. Energy metabolism of cancer cells has become an attractive target for cancer therapy because it is a common phenotypic trait of most carcinomas. In addition, silencing of the H+-ATP synthase in most prevalent carcinomas is also exerted at the activity level by overexpression of the ATPase inhibitory factor 1 (IF1), a protein that contributes to metabolic rewiring and the signaling of cell death-resistant phenotypes in cancer cells.

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Acknowledgments

The authors gratefully acknowledge the work, support, and ideas of many colleagues and collaborators, especially to Drs. María Sánchez-Aragó and Laura Formentini and to the excellent technical support provided by M. Chamorro and C. Nuñez de Arenas over all these years. Work in the authors’ laboratory was supported by grants from the Ministerio de Educación y Ciencia (BFU2010-18903), by the Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER-ISCIII), and by Comunidad de Madrid (S/2011-BMD-2402), Spain. The CBMSO receives an institutional grant from Fundación Ramón Areces.

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  1. Departamento de Biología Molecular, Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid (CSIC-UAM), Centro de Investigación Biomédica en Red de Enfermedades Raras CIBERER-ISCIII, Instituto de Investigación Hospital 12 de Octubre, Universidad Autónoma de Madrid, Madrid, 28049, Spain

    Inmaculada Martínez-Reyes & José M. Cuezva

  2. Centro de Biologia Molecular Severo Ochoa, Universidad Autonoma de Madrid, Nicolas Cabrera 1, Madrid, 28049, Spain

    José M. Cuezva

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  1. Inmaculada Martínez-Reyes
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  2. José M. Cuezva
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Correspondence to José M. Cuezva .

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  1. Inst. of Veterinary Physiology and Bioch, Justus-Liebig-University of Giessen, Gießen, Hessen, Germany

    Sybille Mazurek

  2. Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden

    Maria Shoshan

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Martínez-Reyes, I., Cuezva, J.M. (2015). The Relevance of the Mitochondrial H+-ATP Synthase in Cancer Biology. In: Mazurek, S., Shoshan, M. (eds) Tumor Cell Metabolism. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1824-5_11

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