ALS-linked mutant superoxide dismutase 1 (SOD1) alters mitochondrial protein composition and decreases protein import
Open accessAbstract
Mutations in superoxide dismutase 1 (SOD1) cause familial ALS. Mutant SOD1 preferentially associates with the cytoplasmic face of mitochondria from spinal cords of rats and mice expressing SOD1 mutations. Two-dimensional gels and multidimensional liquid chromatography, in combination with tandem mass spectrometry, revealed 33 proteins that were increased and 21 proteins that were decreased in SOD1(G93A) rat spinal cord mitochondria compared with SOD1(WT) spinal cord mitochondria. Analysis of this group of proteins revealed a higher-than-expected proportion involved in complex I and protein import pathways. Direct import assays revealed a 30% decrease in protein import only in spinal cord mitochondria, despite an increase in the mitochondrial import components TOM20, TOM22, and TOM40. Recombinant SOD1(G93A) or SOD1(G85R), but not SOD1(WT) or a Parkinson's disease-causing, misfolded α-synuclein(E46K) mutant, decreased protein import by >50% in nontransgenic mitochondria from spinal cord, but not from liver. Thus, altered mitochondrial protein content accompanied by selective decreases in protein import into spinal cord mitochondria comprises part of the mitochondrial damage arising from mutant SOD1.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Tom20 and Tom70 have been associated with Parkinson's disease-linked parkin and ALS-linked SOD1.
“Additionally, Tom20 and Tom70 have been associated to Parkinson's disease-linked parkin and ALS-linked SOD1 (64,65).”
From Functional genomic screen and network analysis reveal novel modifiers of tauopathy dissociated from tau phosphorylation (2011) · cites this paper as [65]
The Results report increased TOM20 in spinal-cord mitochondria from rats expressing ALS-linked SOD1 G93A, supporting an association between TOM20 and mutant SOD1. The cited paper's passages identify TOM20, TOM22, and TOM40, but do not establish an association between TOM70 and SOD1. They also do not establish the parkin association, which may be the subject of the sentence's other citation. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Onset and Progression in Inherited ALS Determined by Motor Neurons and Microglia
Boillée, S., Yamanaka, K., Lobsiger, C. S., Copeland, N. G., Jenkins, N. A., Kassiotis, G., Kollias, G., & Cleveland, D. W. (2006) · Science · doi:10.1126/science.1123511 · Cited by 1,623 · see citing works
Self-citationAstrocytes as determinants of disease progression in inherited amyotrophic lateral sclerosis
Yamanaka, K., Chun, S. J., Boillee, S., Fujimori-Tonou, N., Yamashita, H., Gutmann, D. H., Takahashi, R., Misawa, H., & Cleveland, D. W. (2008) · Nature Neuroscience · doi:10.1038/nn2047 · Cited by 1,140 · see citing works
Self-citationDevi, L., Prabhu, B. M., Galati, D. F., Avadhani, N. G., & Anandatheerthavarada, H. K. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.1469-06.2006 · Cited by 792 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Ambegaokar, S. S., & Jackson, G. R. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr432 · Cited by 113 · see citing works
“Additionally, Tom20 and Tom70 have been associated to Parkinson’s disease-linked parkin and ALS-linked SOD1 (64,65).”
BackgroundProteomics Approaches for Biomarker and Drug Target Discovery in ALS and FTD
Hedl, T. J., San Gil, R., Cheng, F., Rayner, S. L., Davidson, J. M., De Luca, A., Villalva, M. D., Ecroyd, H., Walker, A. K., & Lee, A. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00548 · Cited by 87 · see citing works
Dutta, K., Patel, P., & Julien, J.-P. (2018) · Experimental Neurology · doi:10.1016/j.expneurol.2018.08.008 · Cited by 56 · see citing works
- Authors
- Li, Q., Vande Velde, C., Israelson, A., Xie, J., Bailey, A. O., Dong, M.-Q., Chun, S.-J., Roy, T., Winer, L., Yates, J. R., Capaldi, R. A., Cleveland, D. W., & Miller, T. M.
- Affiliations
- Washington University in St. Louis (US)
- Ludwig Institute and Departments of Cellular and Molecular Medicine and Neuroscience, University of California at San Diego, La Jolla, CA 92093-0670;
- University of California San Diego (US)
- MitoSciences, Eugene, OR 97403
- Scripps Research Institute (US)
- Corresponding author
- Li, Quan
- Cleveland, Don W.
- Miller, Timothy M.
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2010-11-15
- Volume
- 107
- Issue
- 49
- Pages
- 21146-21151
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3000256
- OpenAlex
- W2170666584
- Cited by
- 169
- References
- 3
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 6 · 2023: 7 · 2022: 4 · 2021: 18 · 2020: 8 · 2019: 12 · 2018: 9 · 2017: 12 · 2016: 12 · 2015: 11 · 2014: 12 · 2013: 18 · 2012: 16
- FWCI
- 9.35
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust (089701)
- National Institute on Aging (K12AG000975, AG000975)
- National Institute of Neurological Disorders and Stroke (NS 27036, R37NS027036, R01NS027036)
- Topics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- superoxide dismutase 1, SOD1 mutations, amyotrophic lateral sclerosis, familial ALS, mitochondrial protein import, SOD1 G93A, TOM complex, complex I, mitochondrial damage, Parkinson's disease
- MeSH terms
- Superoxide Dismutase-1, Amyotrophic Lateral Sclerosis, Animals, Liver, Mitochondria, Mutation, Spinal Cord, Superoxide Dismutase, Protein Transport, Mitochondrial Proteins, Proteomics, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
