ArticleProceedings of the National Academy of Sciences of the United States of America2023
Mitochondria-associated membrane collapse impairs TBK1-mediated proteostatic stress response in ALS.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 17 citations in OpenAlex.
- TBK1 eliminates aggregation-prone monomeric TDP-43 through an IFNβ-immunoproteasome pathway in ALS models.EMBO reports · 2026Article
- Mitochondria-associated endoplasmic reticulum membranes and calcium ion exchange: A novel direction for aging and neurodegenerative diseases.Neural regeneration research · 2026Article
- Article
- Mitochondria-ER contact sites (MERCS) in the cell cycle: molecular architecture and functional remodeling across cellular states.BMC biology · 2026Review
- Mitochondria-ER contact sites in neurological disorders.Animal cells and systems · 2026Review
- GLP-1 receptor and Mitochondria-ER Contact Sites: an emerging mechanism of metabolic regulation.Frontiers in physiology · 2026Review
- PRMT1 (protein arginine methyltransferase 1) is essential for neuromuscular junction and mitochondrial homeostasis via mitophagy regulation.Autophagy · 2025Article
- Crosstalk Between the Endoplasmic Reticulum and Mitochondria in Skeletal Muscle: Implications for Meat Quality.Animals : an open access journal from MDPI · 2025Review
- Exploring TANK-Binding Kinase 1 in Amyotrophic Lateral Sclerosis: From Structural Mechanisms to Machine Learning-Guided Therapeutics.Life (Basel, Switzerland) · 2025Review
- Amyotrophic Lateral Sclerosis: Focus on Cytoplasmic Trafficking and Proteostasis.Molecular neurobiology · 2025Review
- Mitochondria and Endoplasmic Reticulum Contact Site as a Regulator of Proteostatic Stress Responses in Neurodegenerative Diseases.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Mitochondria-Associated Membranes: A Key Point of Neurodegenerative Diseases.CNS neuroscience & therapeutics · 2025Review
- TBK1 is involved in programmed cell death and ALS-related pathways in novel zebrafish models.Cell death discovery · 2025Article
- The correlation between mitochondria-associated endoplasmic reticulum membranes (MAMs) and CaActa pharmacologica Sinica · 2025Review
- Organellar quality control crosstalk in aging-related disease: Innovation to pave the way.Aging cell · 2025Review
- Ubiquitination regulation of mitochondrial homeostasis: a new sight for the treatment of gastrointestinal tumors.Frontiers in immunology · 2025Review
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
The organelle contact site of the endoplasmic reticulum and mitochondria, known as the mitochondria-associated membrane (MAM), is a multifunctional microdomain in cellular homeostasis. We previously reported that MAM disruption is a common pathological feature in amyotrophic lateral sclerosis (ALS); however, the precise role of MAM in ALS was uncovered. Here, we show that the MAM is essential for TANK-binding kinase 1 (TBK1) activation under proteostatic stress conditions. A MAM-specific E3 ubiquitin ligase, autocrine motility factor receptor, ubiquitinated nascent proteins to activate TBK1 at the MAM, which results in ribosomal protein degradation. MAM or TBK1 deficiency under proteostatic stress conditions resulted in increased cellular vulnerability in vitro and motor impairment in vivo. Thus, MAM disruption exacerbates proteostatic stress via TBK1 inactivation in ALS. Our study has revealed a proteostatic mechanism mediated by the MAM-TBK1 axis, highlighting the physiological importance of the organelle contact sites.
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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.