Cited by 42Mitochondrial Function and PathologyGenetics, Aging, and Longevity in Model OrganismsAutophagy in Disease and Therapy

Loss of the drosophila m-aaa mitochondrial protease paraplegin results in mitochondrial dysfunction, shortened lifespan, and neuronal and muscular degeneration

Open access
Pareek, Gautam, Thomas, Ruth E., Pallanck, Leo J.·2018·Cell Death & Disease

Abstract

Abstract The progressive accumulation of dysfunctional mitochondria is implicated in aging and in common diseases of the elderly. To oppose this occurrence, organisms employ a variety of strategies, including the selective degradation of oxidatively damaged and misfolded mitochondrial proteins. Genetic studies in yeast indicate that the ATPase Associated with diverse cellular Activities (AAA+) family of mitochondrial proteases account for a substantial fraction of this protein degradation, but their metazoan counterparts have been little studied, despite the fact that mutations in the genes encoding these proteases cause a variety of human diseases. To begin to explore the biological roles of the metazoan mitochondrial AAA+ protease family, we have created a CRISPR/Cas9 allele of the Drosophila homolog of SPG7, which encodes an inner membrane-localized AAA+ protease known as paraplegin. Drosophila SPG7 mutants exhibited shortened lifespan, progressive locomotor defects, sensitivity to chemical and environmental stress, and muscular and neuronal degeneration. Ultrastructural examination of photoreceptor neurons indicated that the neurodegenerative phenotype of SPG7 mutants initiates at the synaptic terminal. A variety of mitochondrial defects accompanied the degenerative phenotypes of SPG7 mutants, including altered axonal transport of mitochondria, accumulation of electron-dense material in the matrix of flight muscle mitochondria, reduced activities of respiratory chain complexes I and II, and severely swollen and dysmorphic mitochondria in the synaptic terminals of photoreceptors. Drosophila SPG7 mutants recapitulate key features of human diseases caused by mutations in SPG7, and thus provide a foundation for the identification of Drosophila paraplegin substrates and strategies that could be used to ameliorate the symptoms of these diseases.

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.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/s41419-018-0365-8

Cites

62 of 62 references verified0 citation errors · 0 not checkable

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.

A few free checks a day · papers already verified open instantly · results are public

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?

  • Mutation of Drosophila m-AAA mitochondrial protease leads to impaired mitochondria function, shortened lifespan, and neuronal and muscular degeneration.

    “Mutation of Drosophila m-AAA mitochondrial protease leaded to impaired mitochondria function, shortened lifespan, and neuronal and muscular degeneration (58).”

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

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Pareek, G., Thomas, R. E., & Pallanck, L. J.
Affiliations
University of Washington (US)
Corresponding author
Pallanck, Leo J.
Venue
Cell Death & Disease
Published
2018-02-21
Volume
9
Issue
3
Pages
304-304
ISSN
2041-4889 (ISSN-L)
OpenAlex
W2793832427
Cited by
42
References
61
Citations by year
2026: 3 · 2025: 6 · 2024: 2 · 2023: 8 · 2022: 7 · 2021: 1 · 2020: 6 · 2019: 5 · 2018: 4
FWCI
1.42
Type
journal article
Language
en
Open access
Locations
  • Cell Death and Disease (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • University of Washington
  • National Institutes of Health
  • National Institute of Neurological Disorders and Stroke (R21NS094901)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
Keywords
paraplegin, SPG7, AAA+ protease, mitochondrial proteolysis, mitochondrial dysfunction, Drosophila, lifespan, neurodegeneration, photoreceptors, respiratory chain complexes, mitochondrial ultrastructure, locomotion defects, muscle degeneration, aging, CRISPR/Cas9 mutants
MeSH terms
ATPases Associated with Diverse Cellular Activities, Animals, Axons, Behavior, Animal, Drosophila melanogaster, Electron Transport, Larva, Longevity, Metalloendopeptidases, Mitochondria, Muscles, Mutation, Nerve Degeneration, Synapses, Sequence Homology, Amino Acid, Drosophila Proteins

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