Riera-Borrull M1,2, Rodríguez-Gallego E1,2, Hernández-Aguilera A1,2, Luciano F1,2, Ras R3, Cuyàs E4,5, Camps J1,2, Segura-Carretero A6,7, Menendez JA4,5,Joven J1,2, Fernández-Arroyo S1,2.

  • 1Unitat de Recerca Biomèdica, Hospital Universitari de Sant Joan, IISPV, Universitat Rovira i Virgili, Reus, Spain.
  • 2Campus of International Excellence Southern Catalonia, Tarragona, Spain.
  • 3Center for Omics Sciences, Reus, Spain.
  • 4Metabolism and Cancer Group, Translational Research Laboratory, Catalan Institute of Oncology (ICO), Girona, Spain.
  • 5Girona Biomedical Research Institute (IDIBGI), Girona, Spain.
  • 6Department of Analytical Chemistry, University of Granada, Granada, Spain.
  • 7Research and Development of Functional Food Centre (CIDAF), Granada, Spain.

Abstract

Abnormalities in mitochondrial metabolism and regulation of energy balance contribute to human diseases. The consequences of high fat and other nutrient intake, and the resulting acquired mitochondrial dysfunction, are essential to fully understand common disorders, including obesity, cancer, and atherosclerosis. To simultaneously and noninvasively measure and quantify indirect markers of mitochondrial function, we have developed a method based on gas chromatography coupled to quadrupole-time of flight mass spectrometry and an electron ionization interface, and validated the system using plasma from patients with peripheral artery disease, human cancer cells, and mouse tissues. This approach was used to increase sensibility in the measurement of a wide dynamic range and chemical diversity of multiple intermediate metabolites used in energy metabolism. We demonstrate that our targeted metabolomics method allows for quick and accurate identification and quantification of molecules, including the measurement of small yet significant biological changes in experimental samples. The apparently low process variability required for its performance in plasma, cell lysates, and tissues allowed a rapid identification of correlations between interconnected pathways. Our results suggest that delineating the process of energy generation by targeted metabolomics can be a valid surrogate for predicting mitochondrial dysfunction in biological samples. Importantly, when used in plasma, targeted metabolomics should be viewed as a robust and noninvasive source of biomarkers in specific pathophysiological scenarios.

KEYWORDS:

Arteriosclerosis; Biomarkers; Cancer; Energy metabolism; Gas chromatography; Mitochondrial dysfunction; Targeted metabolomics

PMID:26383735