ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2009
Haploinsufficiency of AFG3L2, the gene responsible for spinocerebellar ataxia type 28, causes mitochondria-mediated Purkinje cell dark degeneration.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 107 citations in OpenAlex.
- Physalin F Promotes AFG3L2-Mediated Degradation of VISA/MAVS to Suppress Innate Immune Response to RNA Virus.Pathogens (Basel, Switzerland) · 2026Article
- Biallelic Variants in AFG3L2 Causing Spastic Ataxia Type 5 (SPAX5): Report of Two Pediatric Cases from Bogotá, Colombia.Movement disorders clinical practice · 2025Article
- Multifaceted Roles of AFG3L2, a Mitochondrial ATPase in Relation to Neurological Disorders.Molecular neurobiology · 2024Review
- Sustained OMA1-mediated integrated stress response is beneficial for spastic ataxia type 5.Brain : a journal of neurology · 2024Article
- Mitochondrial damage and impaired mitophagy contribute to disease progression in SCA6.Acta neuropathologica · 2024Article
- Restoring calcium homeostasis in Purkinje cells arrests neurodegeneration and neuroinflammation in the ARSACS mouse model.JCI insight · 2023Article
- Targeting Ion Channels and Purkinje Neuron Intrinsic Membrane Excitability as a Therapeutic Strategy for Cerebellar Ataxia.Life (Basel, Switzerland) · 2023Review
- Preserving and enhancing mitochondrial function after stroke to protect and repair the neurovascular unit: novel opportunities for nanoparticle-based drug delivery.Frontiers in cellular neuroscience · 2023Review
- Consensus Paper: Strengths and Weaknesses of Animal Models of Spinocerebellar Ataxias and Their Clinical Implications.Cerebellum (London, England) · 2022Article
- Review
- The Role of Mitochondria in Optic Atrophy With Autosomal Inheritance.Frontiers in neuroscience · 2021Review
- Impaired flickering of the permeability transition pore causes SPG7 spastic paraplegia.EBioMedicine · 2020Article
- Inactivation of the mitochondrial protease Afg3l2 results in severely diminished respiratory chain activity and widespread defects in mitochondrial gene expression.PLoS genetics · 2020Article
- Unique Structural Features of the Mitochondrial AAA+ Protease AFG3L2 Reveal the Molecular Basis for Activity in Health and Disease.Molecular cell · 2019Article
- Article
- Pathogenic variants in the AFG3L2 proteolytic domain cause SCA28 through haploinsufficiency and proteostatic stress-driven OMA1 activation.Journal of medical genetics · 2019Article
- Mitochondrial Proteolysis and Metabolic Control.Cold Spring Harbor perspectives in biology · 2019Review
- Motor Performances of Spontaneous and Genetically Modified Mutants with Cerebellar Atrophy.Cerebellum (London, England) · 2019Review
- Loss of the mitochondrialEMBO molecular medicine · 2019Article
- Upregulation of Peroxiredoxin 3 ProtectsOxidative medicine and cellular longevity · 2019Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Paraplegin and AFG3L2 are ubiquitous nuclear-encoded mitochondrial proteins that form hetero-oligomeric paraplegin-AFG3L2 and homo-oligomeric AFG3L2 complexes in the inner mitochondrial membrane, named m-AAA proteases. These complexes ensure protein quality control in the inner membrane, jointly with a chaperone-like activity on the respiratory chain complexes. Despite coassembling in the same complex, mutations of either paraplegin or AFG3L2 cause two different neurodegenerative disorders. Indeed, mutations of paraplegin are responsible for a recessive form of hereditary spastic paraplegia, whereas mutations of AFG3L2 have been recently associated to a dominant form of spinocerebellar ataxia (SCA28). In this work, we report that the mouse model haploinsufficient for Afg3l2 recapitulates important pathophysiological features of the human disease, thus representing the first SCA28 model. Furthermore, we propose a pathogenetic mechanism in which respiratory chain dysfunction and increased reactive oxygen species production caused by Afg3l2 haploinsufficiency lead to dark degeneration of Purkinje cells and cerebellar dysfunction.
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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.