ArticleAging cell2022
Reduced endosomal microautophagy activity in aging associates with enhanced exocyst-mediated protein secretion.
Article in Aging cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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
25 citing papers in PubMed, 27 citations in OpenAlex.
- Chaperone-mediated autophagy in physiological homeostasis, disease and ageing.Nature reviews. Molecular cell biology · 2026Review
- Peptide-mediated inhibition of aberrant chaperone-mediated autophagy in pericytes prevents glioblastoma progression through MAPT/tau secretion.Autophagy · 2026Article
- Review
- Primary cilia-extracellular vesicle crosstalk in Alzheimer's disease: Emerging mechanisms and biomarker potential.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Defining the reference proteomes for small extracellular vesicles and non-vesicular components.Nature cell biology · 2026Article
- Rsp5/NEDD4 and ESCRT regulate TDP-43 toxicity and turnover via an endolysosomal clearance mechanism.The Journal of cell biology · 2026Article
- Microautophagy: current understanding of its molecular mechanisms and functions.Autophagy reports · 2026Review
- Endosomal microautophagy is activated by specific cellular stresses in trout hepatocytes.Scientific reports · 2025Article
- The Proteostasis Network in Proteinopathies: Mechanisms and Interconnections.The American journal of pathology · 2025Review
- HSP70 is a chaperone for IL-33 activity in chronic airway disease.JCI insight · 2025Article
- Lipid Droplet Degradation Through Lipophagy in Aurantiochytrium limacinum mh0186.Marine biotechnology (New York, N.Y.) · 2025Article
- Heat shock proteins function as signaling molecules to mediate neuron-glia communication in C. elegans during aging.Nature neuroscience · 2025Article
- Sex-specific and cell-type-specific changes in chaperone-mediated autophagy across tissues during aging.Nature aging · 2025Article
- Huntingtin contains an ubiquitin-binding domain and regulates lysosomal targeting of mitochondrial and RNA-binding proteins.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- Article
- The Role of Pyroptosis and Autophagy in the Nervous System.Molecular neurobiology · 2024Review
- Heat Shock Proteins Function as Signaling Molecules to Mediate Neuron-Glia Communication During Aging.bioRxiv : the preprint server for biology · 2024Article
- Lysosomes in senescence and aging.EMBO reports · 2023Review
- Human Skin Aging and the Anti-Aging Properties of Retinol.Biomolecules · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 6 institutions in 1 country.
Funding
Abstract
Autophagy is essential for protein quality control and regulation of the functional proteome. Failure of autophagy pathways with age contributes to loss of proteostasis in aged organisms and accelerates the progression of age-related diseases. In this work, we show that activity of endosomal microautophagy (eMI), a selective type of autophagy occurring in late endosomes, declines with age and identify the sub-proteome affected by this loss of function. Proteomics of late endosomes from old mice revealed an aberrant glycation signature for Hsc70, the chaperone responsible for substrate targeting to eMI. Age-related Hsc70 glycation reduces its stability in late endosomes by favoring its organization into high molecular weight protein complexes and promoting its internalization/degradation inside late endosomes. Reduction of eMI with age associates with an increase in protein secretion, as late endosomes can release protein-loaded exosomes upon plasma membrane fusion. Our search for molecular mediators of the eMI/secretion switch identified the exocyst-RalA complex, known for its role in exocytosis, as a novel physiological eMI inhibitor that interacts with Hsc70 and acts directly at the late endosome membrane. This inhibitory function along with the higher exocyst-RalA complex levels detected in late endosomes from old mice could explain, at least in part, reduced eMI activity with age. Interaction of Hsc70 with components of the exocyst-RalA complex places this chaperone in the switch from eMI to secretion. Reduced intracellular degradation in favor of extracellular release of undegraded material with age may be relevant to the spreading of proteotoxicity associated with aging and progression of proteinopathies.
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.