The DOI matches its Crossref record; 53 of the 53 references it cites were found in a registry or an index.
Lon protease preferentially degrades oxidized mitochondrial aconitase by an ATP-stimulated mechanism
Open accessAbstract
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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“aging is associated with impaired activity of the proteasome and mitochondrial Lon proteases [203,204,205] and reduced capacity for macromolecule repair [201,202].”
From Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease (2022) · cites this paper as [204]
In the citing paper
“In mammals, several mitochondrial regulatory proteins such as aconitase (ACO), cytochrome c oxidase isoform (Cox4i1), steroidogenic acute regulatory protein (STAR), and transcription factor A (TFAM) have been identified as LONP1 substrates under basal or stress conditions2,4,16,17.”
From Disuse-associated loss of the protease Lonp1 in muscle impairs mitochondrial function and causes reduced skeletal muscle mass and strength (2022) · cites this paper as [16]
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Metadata
- Authors
- Bota, D. A., & Davies, K. J. A.
- Affiliations
- University of Southern California (US)
- Corresponding author
- Davies, Kelvin J. A.
- Venue
- Nature Cell Biology
- Published
- 2002-08-27
- Volume
- 4
- Issue
- 9
- Pages
- 674-680
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- 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
- 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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