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Lon protease preferentially degrades oxidized mitochondrial aconitase by an ATP-stimulated mechanism

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Bota, Daniela A., Davies, Kelvin J. A.·2002·Nature Cell Biology

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Abstract

Mitochondrial aconitase is sensitive to oxidative inactivation and can aggregate and accumulate in many age-related disorders. Here we report that Lon protease, an ATP-stimulated mitochondrial matrix protein, selectively recognizes and degrades the oxidized, hydrophobic form of aconitase after mild oxidative modification, but that severe oxidation results in aconitase aggregation, which makes it a poor substrate for Lon. Similarly, a morpholino oligodeoxynucleotide directed against the lon gene markedly decreases the amount of Lon protein, Lon activity and aconitase degradation in WI-38 VA-13 human lung fibroblasts and causes accumulation of oxidatively modified aconitase. The ATP-stimulated Lon protease may be an essential defence against the stress of life in an oxygen environment. By recognizing minor oxidative changes to protein structure and rapidly degrading the mildly modified protein, Lon protease may prevent extensive oxidation, aggregation and accumulation of aconitase, which could otherwise compromise mitochondrial function and cellular viability. Aconitase is probably only one of many mitochondrial matrix proteins that are preferentially degraded by Lon protease after oxidative modification.

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Authors: Bota, D. A., & Davies, K. J. A.
Affiliations: University of Southern California (US)
Corresponding author: Davies, Kelvin J. A.
ORCID: Bota, Daniela A.
Davies, Kelvin J. A.
Venue: Nature Cell Biology
Publisher: Springer Science and Business Media LLC
Published: 2002-08-27
Volume: 4
Issue: 9
Pages: 674-680
ISSN: 1465-7392 (ISSN-L)
1476-4679
DOI: 10.1038/ncb836
OpenAlex: W2036284918
Cited by: 557
References: 53
Citations by year: 2026: 15 · 2025: 21 · 2024: 15 · 2023: 19 · 2022: 21 · 2021: 21 · 2020: 21 · 2019: 18 · 2018: 32 · 2017: 26 · 2016: 24 · 2015: 25 · 2014: 25 · 2013: 31 · 2012: 45
FWCI: 4.12
Type: journal article
Language: en
Open access: green
escholarship.org
Licence: cc-by
www.springer.com/tdm (tdm)
Locations: Nature Cell Biology (publishedVersion)
PubMed (publishedVersion)
eScholarship (California Digital Library) (submittedVersion, cc-by)
Funders: National Institutes of Health
National Institute on Aging (R01AG016256, AG16256)
National Institute of Environmental Health Sciences (ES03598)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
Keywords: Lon protease, mitochondrial aconitase, protein oxidation, protein degradation, protein aggregation, mitochondrial matrix, oxidative stress, age-related diseases, WI-38 fibroblasts, mitochondrial function
MeSH terms: Aconitate Hydratase, Adenosine Triphosphate, Animals, Base Sequence, Cattle, Cell Line, Heat-Shock Proteins, Humans, Hydrogen Peroxide, Kinetics, Mitochondria, Mitochondria, Heart, Oxidation-Reduction, Serine Endopeptidases, Oligodeoxyribonucleotides, Antisense, ATP-Dependent Proteases, In Vitro Techniques

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Lon protease preferentially degrades oxidized mitochondrial aconitase by an ATP-stimulated mechanism

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