ArticleCell reports2020
Altered MICOS Morphology and Mitochondrial Ion Homeostasis Contribute to Poly(GR) Toxicity Associated with C9-ALS/FTD.
Article in Cell reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 46 citations in OpenAlex.
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- Mitochondrial Quality Control Impairment Is a Hallmark of TDP-43Antioxidants (Basel, Switzerland) · 2026Article
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- Microglial CARD19 ameliorates post-stroke neuroinflammation by stabilizing mitochondrial cristae.Neural regeneration research · 2026Article
- C9orf72-ALS mutation drives basal mitophagy impairments in iNeurons.Frontiers in cellular neuroscience · 2026Article
- Marf- and Opa1-Dependent Formation of Mitochondrial Network Structure Is Required for Cell Growth and Subsequent Meiosis inInternational journal of molecular sciences · 2025Article
- Nutraceutical Strategies for Targeting Mitochondrial Dysfunction in Neurodegenerative Diseases.Foods (Basel, Switzerland) · 2025Review
- Article
- The 40S ribosomal subunit recycling complex modulates mitochondrial dynamics and endoplasmic reticulum - mitochondria tethering at mitochondrial fission/fusion hotspots.Nature communications · 2025Article
- C9orf72-Associated Dipeptide Repeat Expansions Perturb ER-Golgi Vesicular Trafficking, Inducing Golgi Fragmentation and ER Stress, in ALS/FTD.Molecular neurobiology · 2024Article
- Decoding Nucleotide Repeat Expansion Diseases: Novel Insights fromInternational journal of molecular sciences · 2024Review
- Activation of the Keap1/Nrf2 pathway suppresses mitochondrial dysfunction, oxidative stress, and motor phenotypes inLife science alliance · 2024Article
- Biosensors; a novel concept in real-time detection of autophagy.Biosensors & bioelectronics · 2024Review
- Glucose hypometabolism prompts RAN translation and exacerbates C9orf72-related ALS/FTD phenotypes.EMBO reports · 2024Article
- The IRE1/Xbp1 axis restores ER and tissue homeostasis perturbed by excess Notch in Drosophila.Developmental biology · 2024Article
- Stalled translation by mitochondrial stress upregulates a CNOT4-ZNF598 ribosomal quality control pathway important for tissue homeostasis.Nature communications · 2024Article
- Pectolinarigenin Improves Oxidative Stress and Apoptosis in Mouse NSC-34 Motor Neuron Cell Lines Induced by C9-ALS-Associated Proline-Arginine Dipeptide Repeat Proteins by Enhancing Mitochondrial Fusion Mediated via the SIRT3/OPA1 Axis.Antioxidants (Basel, Switzerland) · 2023Article
- Mitochondrial Cristae Morphology Reflecting Metabolism, Superoxide Formation, Redox Homeostasis, and Pathology.Antioxidants & redox signaling · 2023Review
- Mitochondrial dysfunction in neurodegenerative disorders: Potential therapeutic application of mitochondrial transfer to central nervous system-residing cells.Journal of translational medicine · 2023Review
- Differential toxicity and localization of arginine-richiScience · 2023Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Amyotrophic lateral sclerosis (ALS) manifests pathological changes in motor neurons and various other cell types. Compared to motor neurons, the contribution of the other cell types to the ALS phenotypes is understudied. G4C2 repeat expansion in C9ORF72 is the most common genetic cause of ALS along with frontotemporal dementia (C9-ALS/FTD), with increasing evidence supporting repeat-encoded poly(GR) in disease pathogenesis. Here, we show in Drosophila muscle that poly(GR) enters mitochondria and interacts with components of the Mitochondrial Contact Site and Cristae Organizing System (MICOS), altering MICOS dynamics and intra-subunit interactions. This impairs mitochondrial inner membrane structure, ion homeostasis, mitochondrial metabolism, and muscle integrity. Similar mitochondrial defects are observed in patient fibroblasts. Genetic manipulation of MICOS components or pharmacological restoration of ion homeostasis with nigericin effectively rescue the mitochondrial pathology and disease phenotypes in both systems. These results implicate MICOS-regulated ion homeostasis in C9-ALS pathogenesis and suggest potential new therapeutic strategies.
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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 Socratic graph.