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Cited by 589Redox biology and oxidative stressMitochondrial Function and PathologyNitric Oxide and Endothelin Effects

The DOI matches its Crossref record; 61 of the 61 references it cites were found in a registry or an index.

Aconitase is readily inactivated by peroxynitrite, but not by its precursor, nitric oxide.

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Castro, L, Rodriguez, M, Radi, R·1994·Journal of Biological Chemistry
DOI 10.1016/s0021-9258(18)43894-x
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Abstract

Mitochondrial and cytosolic aconitases have been indicated as major targets of .NO- and O2-.-mediated toxicity in cells due to the oxidant-mediated disruption of the [4Fe-4S] prosthetic group. However, under circumstances in which both .NO and O2-. are generated, their almost diffusion-controlled combination reaction (k = 6.7 x 10(9) M-1 s-1), leading to the formation of peroxynitrite anion (ONOO-), can out-compete the direct reactions of .NO and O2-. with aconitase and even the enzymatic dismutation of O2-. by superoxide dismutase. In this work, we report that ONOO- reacts with isolated pig heart mitochondrial aconitase at 1.4 x 10(5) M-1 s-1, resulting in a significant loss of enzymatic activity. Aconitase activity was totally recovered after postincubation with thiols and ferrous iron, indicating that ONOO- reactions with the enzyme involve the perturbation of the labile Fe alpha to yield the inactive [3Fe-4S] cluster, which is also evident by spectral changes. On the other hand, anaerobic exposure of isolated aconitase to high concentrations of .NO (> 100 microM) led to a moderate inhibition of the enzyme, which could be fully overcome by .NO displacement under an argon-saturated atmosphere, in agreement with the formation of a reversible inhibitory complex between .NO and the active site of aconitase. Superoxide inactivated mitochondrial aconitase at (3.5 +/- 2) x 10(6) M-1 s-1, a reaction rate 3 orders of magnitude slower than its reaction rate with .NO. O2-. could represent the main mechanism of inactivation of the enzyme in systems in which it is formed without significant concomitant production of .NO. Our results imply that the mechanisms by which .NO and O2-. inactivate aconitase in cell systems may not be simple due to their direct reactions with the iron-sulfur cluster, but may rely on the formation of ONOO-.

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Crossref · 10.1016/s0021-9258(18)43894-x

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Show all 61 references

Research works printed but not linked: 5

  1. Ischiropoulos, 1992, Arch. Biochem. Biophys., 310, 352
  2. Matheis, 1985, Am. J. Physiol., 262, H616
  3. Jin, X., Squadrito, L., and Pryor, W. A. (1994) Proc. Natl. Acad. Sci. U. S. A., in press
  4. Barlett, D., Church, D. F., Bounds, P. L., and Koppenol, W. H. (1994) Free Radical Biol. & Med., in press[007f]
  5. Floris, 1993, FEBS Lett., 215, 767

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Metadata

Authors
Castro, L., Rodriguez, M., & Radi, R.
Affiliations
Universidad de la República de Uruguay (UY)
ORCID
Castro, L
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
1994-11
Volume
269
Issue
47
Pages
29409-29415
ISSN
0021-9258 (ISSN-L)
DOI
10.1016/s0021-9258(18)43894-x
OpenAlex
W1505685265
Cited by
589
References
61
Citations by year
2026: 2 · 2025: 4 · 2024: 9 · 2023: 5 · 2022: 4 · 2021: 7 · 2020: 5 · 2019: 11 · 2018: 7 · 2017: 9 · 2016: 6 · 2015: 10 · 2014: 15 · 2013: 14 · 2012: 18
FWCI
15.05
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
Keywords
aconitase, peroxynitrite, nitric oxide, superoxide, iron-sulfur clusters, [4Fe-4S] cluster, enzyme inactivation, mitochondrial aconitase, ferrous iron, oxidative stress
MeSH terms
Aconitate Hydratase, Animals, Iron-Sulfur Proteins, Kinetics, Mitochondria, Heart, Nitrates, Nitric Oxide, Nitroso Compounds, Sulfhydryl Compounds, Swine

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