ArticlePLoS genetics2020
C9orf72/ALFA-1 controls TFEB/HLH-30-dependent metabolism through dynamic regulation of Rag GTPases.
Article in PLoS genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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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.
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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.
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Who cites it
16 citing papers in PubMed, 20 citations in OpenAlex.
- Lysosomal homeostasis at the crossroads of neurodegeneration.The Journal of clinical investigation · 2026Review
- The loss of a ClC anion channel increases life span, health span, and stress resistance by alkalinizing a pair of glial cells inScience advances · 2025Article
- Unraveling Molecular Targets for Neurodegenerative Diseases ThroughInternational journal of molecular sciences · 2025Review
- The post-translational regulation of transcription factor EB (TFEB) in health and disease.EMBO reports · 2023Review
- Mitochondrial Dysfunction in Repeat Expansion Diseases.Antioxidants (Basel, Switzerland) · 2023Review
- The regulatory mechanism and therapeutic potential of transcription factor EB in neurodegenerative diseases.CNS neuroscience & therapeutics · 2023Review
- Simple models to understand complex disease: 10 years of progress fromFrontiers in neuroscience · 2023Review
- The progress inSmall GTPases · 2022Review
- The Interplay Between Autophagy and RNA Homeostasis: Implications for Amyotrophic Lateral Sclerosis and Frontotemporal Dementia.Frontiers in cell and developmental biology · 2022Review
- C9orf72 ALS-FTD: recent evidence for dysregulation of the autophagy-lysosome pathway at multiple levels.Autophagy · 2021Review
- A C. elegans model of C9orf72-associated ALS/FTD uncovers a conserved role for eIF2D in RAN translation.Nature communications · 2021Article
- NDST3 deacetylates α-tubulin and suppresses V-ATPase assembly and lysosomal acidification.The EMBO journal · 2021Article
- Cellular and physiological functions of C9ORF72 and implications for ALS/FTD.Journal of neurochemistry · 2021Review
- TFEB: A Emerging Regulator in Lipid Homeostasis for Atherosclerosis.Frontiers in physiology · 2021Review
- Review
- Modeling neurodegeneration inDisease models & mechanisms · 2020Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Nutrient utilization and energy metabolism are critical for the maintenance of cellular homeostasis. A mutation in the C9orf72 gene has been linked to the most common forms of neurodegenerative diseases that include amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here we have identified an evolutionarily conserved function of C9orf72 in the regulation of the transcription factor EB (TFEB), a master regulator of autophagic and lysosomal genes that is negatively modulated by mTORC1. Loss of the C. elegans orthologue of C9orf72, ALFA-1, causes the nuclear translocation of HLH-30/TFEB, leading to activation of lipolysis and premature lethality during starvation-induced developmental arrest in C. elegans. A similar conserved pathway exists in human cells, in which C9orf72 regulates mTOR and TFEB signaling. C9orf72 interacts with and dynamically regulates the level of Rag GTPases, which are responsible for the recruitment of mTOR and TFEB on the lysosome upon amino acid signals. These results have revealed previously unknown functions of C9orf72 in nutrient sensing and metabolic pathways and suggest that dysregulation of C9orf72 functions could compromise cellular fitness under conditions of nutrient stress.
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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.