Review
Unsuspected task for an old team: Succinate, fumarate and other Krebs cycle acids in metabolic remodeling

https://doi.org/10.1016/j.bbabio.2014.03.013Get rights and content
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Highlights

  • Newly discovered functions of Krebs cycle acids strikes by their importance.

  • Central for cellular bioenergetics, they also act as key signaling molecules.

  • By acting on the expression of genes, they can direct cell remodeling and modeling.

Abstract

Seventy years from the formalization of the Krebs cycle as the central metabolic turntable sustaining the cell respiratory process, key functions of several of its intermediates, especially succinate and fumarate, have been recently uncovered. The presumably immutable organization of the cycle has been challenged by a number of observations, and the variable subcellular location of a number of its constitutive protein components is now well recognized, although yet unexplained. Nonetheless, the most striking observations have been made in the recent period while investigating human diseases, especially a set of specific cancers, revealing the crucial role of Krebs cycle intermediates as factors affecting genes methylation and thus cell remodeling. We review here the recent advances and persisting incognita about the role of Krebs cycle acids in diverse aspects of cellular life and human pathology.

Keywords

Mitochondria
Tricarboxylic acid cycle
Dioxygenase
HIF1α
Histone

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