The redox regulation of intermediary metabolism by a superoxide-aconitase rheostat

Bioessays. 2004 Aug;26(8):894-900. doi: 10.1002/bies.20071.

Abstract

In this article, we discuss a hypothesis to explain the preferential synthesis of the superoxide sensitive form of aconitase in mitochondria and the phenotype observed in manganese superoxide dismutase mutant mice, which show a gross over accumulation of stored fat in liver. The model proposes that intermediary metabolism is redox regulated by mitochondrial superoxide generated during mitochondrial respiration. This regulates the level of reducing equivalents (NADH) entering the electron transport chain (ETC) through the reversible inactivation of mitochondrial aconitase. This control mechanism has a dual function; firstly, it regulates levels of superoxide generated by the ETC and, secondly, it fine-tunes metabolism by channeling citrate either for the production of NADH for energy metabolism or diverting it for the synthesis of fats. In this setting, the mitochondrial redox state influences metabolic decisions via a superoxide-aconitase rheostat.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aconitate Hydratase / metabolism*
  • Animals
  • Citric Acid / metabolism
  • Evolution, Molecular
  • Hydrogen Peroxide / metabolism
  • Mice
  • Mice, Knockout
  • Mitochondria / metabolism*
  • Oxidants / metabolism
  • Oxidation-Reduction
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / physiology
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism
  • Superoxides / metabolism*

Substances

  • Oxidants
  • Reactive Oxygen Species
  • Superoxides
  • Citric Acid
  • Hydrogen Peroxide
  • Superoxide Dismutase
  • Aconitate Hydratase