IMR Press / FBL / Volume 14 / Issue 11 / DOI: 10.2741/3509

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Mitochondria: from bioenergetics to the metabolic regulation of carcinogenesis
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1 INSERM U688, Bordeaux, France
2 INSERM U889, Bordeaux, France
3 Universite Victor Segalen Bordeaux 2, 146 rue Leo Saignat, 33076 Bordeaux, France

Academic Editor: Didier Wion

Front. Biosci. (Landmark Ed) 2009, 14(11), 4015–4034; https://doi.org/10.2741/3509
Published: 1 January 2009
(This article belongs to the Special Issue Cancer cell biology)
Abstract

In this review, we discuss the concept of metabolic remodeling and signaling in tumors, specifically the various metabolites that participate in the regulation of gene expression in cancer cells. In particular, pyruvate, oxaloacetate, succinate and fumarate, four mitochondrial metabolites, activate genes relevant for tumor progression. When the balance between glycolysis and oxidative phosphorylation is altered, these metabolites accumulate in the cytoplasm and regulate the activity of the Hypoxia Inducible Factor 1alpha (HIF-1alpha). HIF is one of the main factors that orchestrate the metabolic switch observed during oncogenesis. There is also an important role for lactate, fructose 1-6 bisphosphate or citrate that leads to the diversion of glucose metabolites to anabolism. In addition reactive oxygen species, which are produced by the respiratory chain, could serve as an endogenous source of DNA-damaging agents to promote genetic instability. Accordingly, several mitochondrial DNA mutations were reported in tumors, and the construction of cybrids recently demonstrated their role in the control of tumor progression.

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