Evidence map›Paper›PMID 28792845›Full record

ArticleAutophagy2017

Discovery of pan autophagy inhibitors through a high-throughput screen highlights macroautophagy as an evolutionarily conserved process across 3 eukaryotic kingdoms.

Piyush Mishra, Adrian N Dauphinee, Carl Ward, Sovan Sarkar, Arunika H L A N Gunawardena, Ravi Manjithaya

Open access · hybridAbstract read
In one paragraph

Article in Autophagy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
2.1field-weighted citation impact, top 13% 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

10 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Chemical Biology Strategies to Study Autophagy.Frontiers in cell and developmental biology · 2018
    Review
  10. 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

6 authors at 3 institutions in 3 countries.

Piyush Mishraa Molecular Biology and Genetics Unit , Jawaharlal Nehru Centre for Advanced Scientific Research , Jakkur, Bangalore , India.
Adrian N Dauphineeb Biology Department, Life Sciences Centre , Dalhousie University , Halifax , NS , Canada.
Carl Wardc Institute of Cancer and Genomic Sciences, Institute of Biomedical Research, College of Medical and Dental Sciences , University of Birmingham , Edgbaston, Birmingham , UK.
Sovan Sarkarc Institute of Cancer and Genomic Sciences, Institute of Biomedical Research, College of Medical and Dental Sciences , University of Birmingham , Edgbaston, Birmingham , UK.
Arunika H L A N Gunawardenab Biology Department, Life Sciences Centre , Dalhousie University , Halifax , NS , Canada.
Ravi Manjithayaa Molecular Biology and Genetics Unit , Jawaharlal Nehru Centre for Advanced Scientific Research , Jakkur, Bangalore , India.
Dalhousie University · CAJawaharlal Nehru Centre for Advanced Scientific Research · INUniversity of Birmingham · GB

Funding

DBT-Wellcome Trust India Alliance 500159-Z-09-Z
6 · The paper itself

Abstract

Due to the involvement of macroautophagy/autophagy in different pathophysiological conditions such as infections, neurodegeneration and cancer, identification of novel small molecules that modulate the process is of current research and clinical interest. In this work, we developed a luciferase-based sensitive and robust kinetic high-throughput screen (HTS) of small molecules that modulate autophagic degradation of peroxisomes in the budding yeast Saccharomyces cerevisiae. Being a pathway-specific rather than a target-driven assay, we identified small molecule modulators that acted at key steps of autophagic flux. Two of the inhibitors, Bay11 and ZPCK, obtained from the screen were further characterized using secondary assays in yeast. Bay11 inhibited autophagy at a step before fusion with the vacuole whereas ZPCK inhibited the cargo degradation inside the vacuole. Furthermore, we demonstrated that these molecules altered the process of autophagy in mammalian cells as well. Strikingly, these molecules also modulated autophagic flux in a novel model plant, Aponogeton madagascariensis. Thus, using small molecule modulators identified by using a newly developed HTS autophagy assay, our results support that macroautophagy is a conserved process across fungal, animal and plant kingdoms.

Indexed as

AutophagyBiological EvolutionAmino Acid Chloromethyl KetonesAnimalsAutophagosomesEmbryo, MammalianEnzyme AssaysEukaryotic CellsFibroblastsHeLa CellsHigh-Throughput Screening AssaysHumansLuciferasesMagnoliopsidaMiceModels, Biological3-(4-methylphenylsulfonyl)-2-propenenitrileAmino Acid Chloromethyl KetonesLuciferasesNitrilesSmall Molecule LibrariesSulfonesZPCKautophagic fluxautophagyhigh-throughput screeningkingdomsperoxisomeprogrammed cell deathsmall molecules

Identifiers

PMID28792845
PMCPMC5612355
OpenAlexW2743937374

What OpenQuestion holds

Textmetadata
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.