ArticleNature genetics2010
Mutations in the mitochondrial protease gene AFG3L2 cause dominant hereditary ataxia SCA28.
Article in Nature genetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 163 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
163 citing papers in PubMed, 1 synthesis or guideline pooled it, 341 citations in OpenAlex.
- Targeting Mitochondrial Oxidative Phosphorylation Eradicates Acute Myeloid Leukemic Stem Cells.Frontiers in oncology · 2022Pooled it
- RareInternational journal of molecular sciences · 2026Article
- Loss of Function of AFG3L2 Leading to Developmental and Epileptic Encephalopathy.CNS neuroscience & therapeutics · 2026Article
- Expanding theNeurology. Genetics · 2026Article
- Purkinje cell intrinsic activity shapes cerebellar development and function.Nature communications · 2026Article
- Molecular mechanisms of mitochondrial AAA+ proteases.The Journal of biological chemistry · 2026Review
- Molecular characterization of recessively inherited ataxic and neuropathic disorders in consanguineous Pakistani families.Scientific reports · 2026Article
- Editorial: Proteostasis disruption in neurodegenerative disorders: mechanisms and treatment strategies.Frontiers in molecular neuroscience · 2026Article
- 3-Methyl Glutaconic Aciduria and Elevated Plasma Growth Differentiation Factor 15 Level in an Adult with MonoallelicActa myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology · 2025Article
- Ecm19 coordinates mitochondrial fission and cellular redox homeostasis.Redox report : communications in free radical research · 2025Article
- Identification of a NovelGenes · 2025Article
- Molecular hallmarks of neurodegeneration in polyglutamine spinocerebellar ataxias.Cell death & disease · 2025Review
- The Neuro-Ophthalmologic Manifestations ofJournal of personalized medicine · 2025Review
- Quality control at the powerhouse: mitochondrial proteostasis dysfunction and disease.Biochemical Society transactions · 2025Article
- Maintaining the Integral Membrane Proteome: Revisiting the Functional Repertoire of Integral Membrane Proteases.Chembiochem : a European journal of chemical biology · 2025Review
- Compound heterozygous mutation of AFG3L2 causes autosomal recessive spinocerebellar ataxia through mitochondrial impairment and MICU1 mediated CaScience China. Life sciences · 2025Article
- Genetic modeling of degenerative diseases and mechanisms of neuronal regeneration in the zebrafish cerebellum.Cellular and molecular life sciences : CMLS · 2024Review
- Mitochondrial Parkinsonism: A Practical Guide to Genes and Clinical Diagnosis.Movement disorders clinical practice · 2024Review
- Dystonia and mitochondrial disease: the movement disorder connection revisited in 900 genetically diagnosed patients.Journal of neurology · 2024Article
- Multifaceted Roles of AFG3L2, a Mitochondrial ATPase in Relation to Neurological Disorders.Molecular neurobiology · 2024Review
103 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
26 authors at 6 institutions in 2 countries.
Funding
Abstract
Autosomal dominant spinocerebellar ataxias (SCAs) are genetically heterogeneous neurological disorders characterized by cerebellar dysfunction mostly due to Purkinje cell degeneration. Here we show that AFG3L2 mutations cause SCA type 28. Along with paraplegin, which causes recessive spastic paraplegia, AFG3L2 is a component of the conserved m-AAA metalloprotease complex involved in the maintenance of the mitochondrial proteome. We identified heterozygous missense mutations in five unrelated SCA families and found that AFG3L2 is highly and selectively expressed in human cerebellar Purkinje cells. m-AAA-deficient yeast cells expressing human mutated AFG3L2 homocomplex show respiratory deficiency, proteolytic impairment and deficiency of respiratory chain complex IV. Structure homology modeling indicates that the mutations may affect AFG3L2 substrate handling. This work identifies AFG3L2 as a novel cause of dominant neurodegenerative disease and indicates a previously unknown role for this component of the mitochondrial protein quality control machinery in protecting the human cerebellum against neurodegeneration.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.