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Cited by 241Mitochondrial Function and PathologyMetalloenzymes and iron-sulfur proteinsRedox biology and oxidative stress

Redox-Dependent Modulation of Aconitase Activity in Intact Mitochondria

Bulteau, Anne-Laure, Ikeda-Saito, Masao, Szweda, Luke I.·2003·Biochemistry
DOI 10.1021/bi0353979
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Abstract

It has previously been reported that exposure of purified mitochondrial or cytoplasmic aconitase to superoxide (O(2)(-)(*) or hydrogen peroxide (H(2)O(2)) leads to release of the Fe-alpha from the enzyme's [4Fe-4S](2+) cluster and to inactivation. Nevertheless, little is known regarding the response of aconitase to pro-oxidants within intact mitochondria. In the present study, we provide evidence that aconitase is rapidly inactivated and subsequently reactivated when isolated cardiac mitochondria are treated with H(2)O(2). Reactivation of the enzyme is dependent on the presence of the enzyme's substrate, citrate. EPR spectroscopic analysis indicates that enzyme inactivation precedes release of the labile Fe-alpha from the enzyme's [4Fe-4S](2+) cluster. In addition, as judged by isoelectric focusing gel electrophoresis, the relative level of Fe-alpha release and cluster disassembly does not reflect the magnitude of enzyme inactivation. These observations suggest that some form of posttranslational modification of aconitase other than release of iron is responsible for enzyme inactivation. In support of this conclusion, H(2)O(2) does not exert its inhibitory effects by acting directly on the enzyme, rather inactivation appears to result from interaction(s) between aconitase and a mitochondrial membrane component responsive to H(2)O(2). Nevertheless, prolonged exposure of mitochondria to steady-state levels of H(2)O(2) or O(2)(-)(*) results in disassembly of the [4Fe-4S](2+) cluster, carbonylation, and protein degradation. Thus, depending on the pro-oxidant species, the level and duration of the oxidative stress, and the metabolic state of the mitochondria, aconitase may undergo reversible modulation in activity or progress to [4Fe-4S](2+) cluster disassembly and proteolytic degradation.

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Authors
Bulteau, A.-L., Ikeda-Saito, M., & Szweda, L. I.
Affiliations
  • Institute of Multidisciplinary Research for Advanced Materials, Tohoku University (JP)
  • Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106-4970, and Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, Katahira, Aoba-ku, Sendai 980-8577, Japan
ORCID
Venue
Biochemistry
Publisher
American Chemical Society (ACS)
Published
2003-11-26
Volume
42
Issue
50
Pages
14846-14855
ISSN
  • 0006-2960 (ISSN-L)
  • 1520-4995
DOI
10.1021/bi0353979
OpenAlex
W1993893812
Cited by
241
References
30
Citations by year
2026: 3 · 2025: 8 · 2024: 7 · 2023: 7 · 2022: 2 · 2021: 7 · 2020: 10 · 2019: 4 · 2018: 8 · 2017: 11 · 2016: 15 · 2015: 13 · 2014: 9 · 2013: 16 · 2012: 17
FWCI
3.45
Type
journal article
Language
en
Open access
closed
Locations
  • Biochemistry (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute on Aging (AG-16339, R01AG016339)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Physical Sciences › Energy › Renewable Energy, Sustainability and the Environment › Metalloenzymes and iron-sulfur proteins
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Keywords
aconitase, [4Fe-4S] cluster, hydrogen peroxide, superoxide, enzyme inactivation, enzyme reactivation, citrate, post-translational modification, carbonylation, protein degradation, oxidative stress, heart mitochondria
MeSH terms
Aconitate Hydratase, Animals, Enzyme Activation, Hydrogen Peroxide, Hydrolysis, Iron-Sulfur Proteins, Male, Mitochondria, Heart, Oxidation-Reduction, Endopeptidases, Rotenone, Superoxides, Oxidants, Rats, Sprague-Dawley, Oxidative Stress, Rats

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