Evidence map›Paper›PMID 34884727›Full record

ArticleInternational journal of molecular sciences2021

Drug-Induced Lysosomal Impairment Is Associated with the Release of Extracellular Vesicles Carrying Autophagy Markers.

Krizia Sagini, Sandra Buratta, Federica Delo, Roberto Maria Pellegrino, Stefano Giovagnoli, Lorena Urbanelli, Carla Emiliani

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.2field-weighted citation impact, top 21% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 24 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Alpha-Synuclein Inhibits the Secretion of Extracellular Vesicles through Disruptions in YKT6 Lipidation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025
    Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Autophagy and autophagy-related pathways in cancer.Nature reviews. Molecular cell biology · 2023
    Review
  12. Article
  13. Review
  14. Review
  15. Review
  16. In Vitro Models for Studying Chronic Drug-Induced Liver Injury.International journal of molecular sciences · 2022
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 2 countries.

Krizia SaginiDepartment of Chemistry, Biology and Biotechnology, University of Perugia, 06123 Perugia, Italy.ORCID 0000-0003-3357-2171
Sandra BurattaDepartment of Chemistry, Biology and Biotechnology, University of Perugia, 06123 Perugia, Italy.
Federica DeloDepartment of Chemistry, Biology and Biotechnology, University of Perugia, 06123 Perugia, Italy.ORCID 0000-0003-0899-2975
Roberto Maria PellegrinoDepartment of Chemistry, Biology and Biotechnology, University of Perugia, 06123 Perugia, Italy.ORCID 0000-0001-5594-383X
Stefano GiovagnoliDepartment of Pharmaceutical Sciences, University of Perugia, 06126 Perugia, Italy.ORCID 0000-0001-5043-7233
Lorena UrbanelliDepartment of Chemistry, Biology and Biotechnology, University of Perugia, 06123 Perugia, Italy.ORCID 0000-0003-0621-8476
Carla EmilianiDepartment of Chemistry, Biology and Biotechnology, University of Perugia, 06123 Perugia, Italy.
University of Perugia · ITCedars-Sinai Medical Center · US

Funding

University of Perugia, Dept of Chemistry, Biology and Biotechnology Ricerca di Base 2019/Urbanelli
6 · The paper itself

Abstract

Amiodarone is a cationic amphiphilic drug used as an antiarrhythmic agent. It induces phospholipidosis, i.e., the accumulation of phospholipids within organelles of the endosomal-lysosomal system. Extracellular vesicles (EVs) are membrane-enclosed structures released by any type of cell and retrieved in every fluid of the body. EVs have been initially identified as a system to dispose cell waste, but they are also considered to be an additional manner to transmit intercellular signals. To understand the role of EVs in drug-induced phospholipidosis, we investigated EVs release in amiodarone-treated HEK-293 cells engineered to produce fluorescently labelled EVs. We observed that amiodarone induces the release of a higher number of EVs, mostly of a large/medium size. EVs released upon amiodarone treatment do not display significant morphological changes or altered size distribution, but they show a dose-dependent increase in autophagy associated markers, indicating a higher release of EVs with an autophagosome-like phenotype. Large/medium EVs also show a higher content of phospholipids. Drugs inducing lysosomal impairment such as chloroquine and bafilomycin A1 similarly prompt a higher release of EVs enriched in autophagy markers. This result suggests a mechanism associated with amiodarone-induced lysosomal impairment more than a connection with the accumulation of specific undigested substrates. Moreover, the implementation of the lysosomal function by overexpressing TFEB, a master gene regulator of lysosomal biogenesis, prevents the amiodarone-induced release of EVs, suggesting that this could be a feasible target to attenuate drug-induced abnormalities.

Indexed as

AmiodaroneAnti-Arrhythmia AgentsAutophagyBiomarkersExtracellular VesiclesHEK293 CellsHumansLysosomesPhospholipidsAmiodaroneAnti-Arrhythmia AgentsBiomarkersPhospholipidsamiodaronebafilomycin A1chloroquineexosomesextracellular vesicleslysosomal storage disordersmicrovesiclesphospholipidosissecretory autophagyTFEB

Identifiers

PMID34884727
PMCPMC8657686
OpenAlexW3215151021

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.