Hypothesis

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

  1. Jeffrey S. Armstrong1,*,
  2. Matthew Whiteman1,
  3. Hongyuan Yang1,
  4. Dean P. Jones2

Article first published online: 19 JUL 2004

DOI: 10.1002/bies.20071

Issue

BioEssays

BioEssays

Volume 26, Issue 8, pages 894–900, August 2004

Additional Information

How to Cite

Armstrong, J. S., Whiteman, M., Yang, H. and Jones, D. P. (2004), The redox regulation of intermediary metabolism by a superoxide–aconitase rheostat. BioEssays, 26: 894–900. doi: 10.1002/bies.20071

Author Information

  1. 1

    Department of Biochemistry, Faculty of Medicine, National University of Singapore, Republic of Singapore

  2. 2

    Department of Medicine, Faculty of Medicine, Emory University, Atlanta, USA

*Department of Biochemistry Faculty of Medicine National University of Singapore, 8 Medical Drive, Singapore 117597.

Publication History

  1. Issue published online: 19 JUL 2004
  2. Article first published online: 19 JUL 2004

Funded by

  • The National Medical Research Council of Singapore. Grant Numbers: #R-183-000-103-112 (JSA), #0474/2000, 0481/2000, 0635/2002 (MW)

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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. BioEssays 26:894–900, 2004. © 2004 Wiley Periodicals, Inc.

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