ArticleCellular and molecular life sciences : CMLS2016
PIKfyve inhibition increases exosome release and induces secretory autophagy.
Article in Cellular and molecular life sciences : CMLS, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 158 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
158 citing papers in PubMed, 256 citations in OpenAlex.
- Generating exosome subtypes: diverse membrane origins and mergers.Trends in cell biology · 2026Review
- Review
- Article
- Cholesteryl esters and high protein-to-lipid ratios distinguish non-vesicular extracellular particles from extracellular vesicles.Cell communication and signaling : CCS · 2026Article
- Two Routes for Removing Unhealthy Mitochondria: Degradation and Secretion.Circulation research · 2026Review
- Applications of extracellular vesicles in tissue regeneration: a narrative review.Frontiers in bioengineering and biotechnology · 2026Review
- Microautophagy: current understanding of its molecular mechanisms and functions.Autophagy reports · 2026Review
- Targeting the secretory autophagy-extracellular vesicle interface: fate decisions and translational opportunities.Frontiers in pharmacology · 2026Review
- The Impact of Neurotoxin Proteins Trafficked by Primary Cilia and Extracellular Vesicles in Neurodegenerative Diseases.Biology · 2025Review
- Placenta-derived extracellular vesicles in fetal health: emerging insights into brain development and environmental interactions.Experimental & molecular medicine · 2025Review
- Clinical relevance of extracellular vesicles in cancer - therapeutic and diagnostic potential.Nature reviews. Clinical oncology · 2025Review
- Synergistic Upregulation of Extracellular Vesicles and Cell-Free Nucleic Acids by Chloroquine and Temozolomide in Glioma Cell Cultures.International journal of molecular sciences · 2025Article
- Autophagic stress activates distinct compensatory secretory pathways in neurons.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Extracellular Vesicles in cancer: from isolation and characterization to metastasis, drug resistance, and clinical applications.BMC cancer · 2025Review
- Extracellular vesicles in TDP-43 proteinopathies: pathogenesis and biomarker potential.Molecular neurodegeneration · 2025Review
- Extracellular Vesicle Lipids and Their Role in Delivery.Journal of extracellular biology · 2025Review
- Exosome: an overview on enhanced biogenesis by small molecules.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Native and Engineered Extracellular Vesicles for the Treatment of Acute Lung Injury and Acute Respiratory Distress Syndrome.Small science · 2025Article
- Autophagy and exosome dynamics in Radiation-Induced pulmonary fibrosis: the critical role of TRIB3.Respiratory research · 2025Article
- Extracellular Vesicles in the Crosstalk of Autophagy and Apoptosis: A Role for Lipid Rafts.Cells · 2025Review
98 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Exosomes are vesicles released from cells by fusion of multivesicular bodies (MVBs) with the plasma membrane. This study aimed to investigate whether the phosphoinositide kinase PIKfyve affects this process. Our results show that in PC-3 cells inhibition of PIKfyve by apilimod or depletion by siRNA increased the secretion of the exosomal fraction. Moreover, quantitative electron microscopy analysis showed that cells treated with apilimod contained more MVBs per cell and more intraluminal vesicles per MVB. Interestingly, mass spectrometry analysis revealed a considerable enrichment of autophagy-related proteins (NBR1, p62, LC3, WIPI2) in exosomal fractions released by apilimod-treated cells, a result that was confirmed by immunoblotting. When the exosome preparations were investigated by electron microscopy a small population of p62-labelled electron dense structures was observed together with CD63-containing exosomes. The p62-positive structures were found in less dense fractions than exosomes in density gradients. Inside the cells, p62 and CD63 were found in the same MVB-like organelles. Finally, both the degradation of EGF and long-lived proteins were shown to be reduced by apilimod. In conclusion, inhibition of PIKfyve increases secretion of exosomes and induces secretory autophagy, showing that these pathways are closely linked. We suggest this is due to impaired fusion of lysosomes with both MVBs and autophagosomes, and possibly increased fusion of MVBs with autophagosomes, and that the cells respond by secreting the content of these organelles to maintain cellular homeostasis.
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.