Mitochondria-mediated energy adaption in cancer: the H(+)-ATP synthase-geared switch of metabolism in human tumors.
CONCLUSIONS
Since the signing of the National Cancer Act in 1971, cancer still remains a major cause of death despite significant progresses made in understanding the biology and treatment of the disease. After many years of ostracism, the peculiar energy metabolism of tumors has been recognized as an additional phenotypic trait of the cancer cell.


BACKGROUND
While the enhanced aerobic glycolysis of carcinomas has already been translated to bedside for precise tumor imaging and staging of cancer patients, accepting that an impaired bioenergetic function of mitochondria is pivotal to understand energy metabolism of tumors and in its progression is debated. However, mitochondrial bioenergetics and cell death are tightly connected.


RESULTS
Recent clinical findings indicate that H(+)-ATP synthase, a core component of mitochondrial oxidative phosphorylation, is repressed at both the protein and activity levels in human carcinomas. This review summarizes the relevance that mitochondrial function has to understand energy metabolism of tumors and explores the connection between the bioenergetic function of the organelle and the activity of mitochondria as tumor suppressors.


CONCLUSIONS
The reversible nature of energy metabolism in tumors highlights the relevance that the microenvironment has for tumor progression. Moreover, the stimulation of mitochondrial activity or the inhibition of glycolysis suppresses tumor growth. Future research should elucidate the mechanisms promoting the silencing of oxidative phosphorylation in carcinomas. The aim is the development of new therapeutic strategies tackling energy metabolism to eradicate tumors or at least, to maintain tumor dormancy and transform cancer into a chronic disease.
Departamento de Biología Molecular, Centro de Biología Molecular Severo Ochoa, Centro de Investigación Biomédica en Red de Enfermedades Raras, Centro de Investigación Hospital 12 de Octubre, Madrid, Spain.
María
M
Sánchez-Aragó
Laura
L
Formentini
José M
JM
Cuezva
D000818:Animals; D002277:Carcinoma / Q000378:metabolism; D016923:Cell Death; D004734:Energy Metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D025261:Mitochondrial Proton-Translocating ATPases / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D059016:Tumor Microenvironment; D025521:Tumor Suppressor Proteins / Q000378:metabolism
D025521:Tumor Suppressor Proteins; D025261:Mitochondrial Proton-Translocating ATPases