Clinical and Translational Oncology

, Volume 19, Issue 4, pp 409–418 | Cite as

Spotlight on the relevance of mtDNA in cancer

  • A. Cruz-Bermúdez
  • R. J. Vicente-Blanco
  • E. Gonzalez-Vioque
  • M. Provencio
  • M. Á. Fernández-Moreno
  • R. Garesse
Review Article


The potential role of the mitochondrial genome has recently attracted interest because of its high mutation frequency in tumors. Different aspects of mtDNA make it relevant for cancer‘s biology, such as it encodes a limited but essential number of genes for OXPHOS biogenesis, it is particularly susceptible to mutations, and its copy number can vary. Moreover, most ROS in mitochondria are produced by the electron transport chain. These characteristics place the mtDNA in the center of multiple signaling pathways, known as mitochondrial retrograde signaling, which modifies numerous key processes in cancer. Cybrid studies support that mtDNA mutations are relevant and exert their effect through a modification of OXPHOS function and ROS production. However, there is still much controversy regarding the clinical relevance of mtDNA mutations. New studies should focus more on OXPHOS dysfunction associated with a specific mutational signature rather than the presence of mutations in the mtDNA.


Cancer Warburg effect Mitochondria mtDNA OXPHOS ROS 



Oxidative phosphorylation


Reactive oxygen species


Mitochondrial DNA



Work in the authors’ laboratories is supported by “Instituto de Salud Carlos III” [PI13/01806 and PIE14/0064 to M.P., PI10/0703 and PI13/00556 to R.G. and PI04/1001 to M.A.F.M.]; “Comunidad Autónoma de Madrid” [S2010/BMD-2402 to R.G.]; “Fundación Mutua Madrileña” [ to M.A.F.M.]. We thank Dr. Bruno Sainz Jr. for helpful suggestions to the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.


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© Federación de Sociedades Españolas de Oncología (FESEO) 2016

Authors and Affiliations

  1. 1.Departamento de Bioquímica and Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER)Facultad de Medicina, UAMMadridSpain
  2. 2.Instituto de Investigaciones Biomédicas “Alberto Sols”, Consejo Superior de Investigaciones Científicas (CSIC)Universidad Autónoma de Madrid (UAM)MadridSpain
  3. 3.Servicio de Oncología Médica, Instituto de Investigación Sanitaria Puerta de HierroHospital Universitario Puerta de Hierro-MajadahondaMadridSpain
  4. 4.Servicio de Bioquímica, Instituto de Investigación Sanitaria Puerta de HierroHospital Universitario Puerta de Hierro-MajadahondaMadridSpain
  5. 5.Instituto de Investigación Sanitaria Hospital 12 de Octubre (i+12)MadridSpain

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