Title:Mitochondrial Proteins as Metabolic Biomarkers and Sites for Therapeutic
Intervention in Primary and Metastatic Cancers
Volume: 24
Issue: 12
Author(s): Diana Xochiquetzal Robledo-Cadena*, Silvia Cecilia Pacheco-Velazquez, Jorge Luis Vargas-Navarro, Joaquín Alberto Padilla-Flores, Rafael Moreno-Sanchez and Sara Rodríguez-Enríquez*
Affiliation:
- Departamento de Bioquímica. Instituto Nacional de Cardiología. Juan Badiano No. 1. Col. Sección XVI. 14080.
Ciudad de México, México
- Posgrado en Ciencias Biológicas, Universidad Nacional Autónoma de México (UNAM),
Coyoacán, México City, 04510, México
- Laboratorio de Control Metabólico, Carrera
de Medicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Los Reyes Ixtacala,
Hab Los Reyes Ixtacala Barrio de los Árboles/Barrio de los Héroes, Tlalnepantla, 54090, México
Keywords:
Metabolic biomarker, oxidative phosphorylation, cancer mitochondria, mitochondrial proteins, anti-mitochondrial therapy.
Abstract: Accelerated aerobic glycolysis is one of the main metabolic alterations in cancer, associated
with malignancy and tumor growth. Although glycolysis is one of the most studied properties
of tumor cells, recent studies demonstrate that oxidative phosphorylation (OxPhos) is the main ATP
provider for the growth and development of cancer. In this last regard, the levels of mRNA and protein
of OxPhos enzymes and transporters (including glutaminolysis, acetate and ketone bodies catabolism,
free fatty acid β-oxidation, Krebs Cycle, respiratory chain, phosphorylating system- ATP
synthase, ATP/ADP translocator, Pi carrier) are altered in tumors and cancer cells in comparison to
healthy tissues and organs, and non-cancer cells. Both energy metabolism pathways are tightly regulated
by transcriptional factors, oncogenes, and tumor-suppressor genes, all of which dictate their
protein levels depending on the micro-environmental conditions and the type of cancer cell, favoring
cancer cell adaptation and growth. In the present review paper, variation in the mRNA and protein
levels as well as in the enzyme/ transporter activities of the OxPhos machinery is analyzed. An
integral omics approach to mitochondrial energy metabolism pathways may allow for identifying
their use as suitable, reliable biomarkers for early detection of cancer development and metastasis,
and for envisioned novel, alternative therapies.
