Evidence map›Paper›PMID 36434621›Full record

ArticleCell communication and signaling : CCS2022

Intracellular cholesterol transport inhibition Impairs autophagy flux by decreasing autophagosome-lysosome fusion.

Yunash Maharjan, Raghbendra Kumar Dutta, Jinbae Son, Xiaofan Wei, Channy Park, Hyug Moo Kwon, Raekil Park

Open access · goldAbstract readVideo-Audio Media
In one paragraph

Article in Cell communication and signaling : CCS, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 1 pooled it
4.4field-weighted citation impact, top 5% 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

24 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.

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  20. Translational cancer research · 2024
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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.

Yunash Maharjan *Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, 61005, Republic of Korea.
Raghbendra Kumar Dutta *Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, 61005, Republic of Korea.
Jinbae SonDepartment of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, 61005, Republic of Korea.
Xiaofan WeiDepartment of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, 61005, Republic of Korea.
Channy ParkDepartment of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, 61005, Republic of Korea.
Hyug Moo KwonSchool of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea.
Raekil ParkDepartment of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, 61005, Republic of Korea. rkpark@gist.ac.kr.
Gwangju Institute of Science and Technology · KRUlsan National Institute of Science and Technology · KR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAutophagy is an intracellular degradation process crucial for homeostasis. During autophagy, a double-membrane autophagosome fuses with lysosome through SNARE machinery STX17 to form autolysosome for degradation of damaged organelle. Whereas defective autophagy enhances cholesterol accumulation in the lysosome and impaired autophagic flux that results Niemann-Pick type C1 (NPC1) disease. However, exact interconnection between NPC1 and autophagic flux remain obscure due to the existence of controversial reports.

resultsThis study aimed at a comparison of the effects of three autophagic inhibitor drugs, including chloroquine, U18666A, and bafilomycin A1, on the intracellular cholesterol transport and autophagy flux. Chloroquine, an autophagic flux inhibitor; U1866A, a NPC1 inhibitor, and bafilomycin A, a lysosomotropic agent are well known to inhibit autophagy by different mechanism. Here we showed that treatment with U1866A and bafilomycin A induces lysosomal cholesterol accumulation that prevented autophagic flux by decreasing autophagosome-lysosome fusion. We also demonstrated that accumulation of cholesterol within the lysosome did not affect lysosomal pH. Although the clearance of accumulated cholesterol by cyclodextrin restored the defective autophagosome-lysosome fusion, the autophagy flux restoration was possible only when lysosomal acidification was not altered. In addition, a failure of STX17 trafficking to autophagosomes plays a key role in prevention of autophagy flux caused by intracellular cholesterol transport inhibitors.

conclusionsOur data provide a new insight that the impaired autophagy flux does not necessarily result in lysosomal cholesterol accumulation even though it prevents autophagosome-lysosome fusion. Video abstract.

Indexed as

AutophagosomesAutophagyChloroquineCholesterolLysosomesMacrolidesbafilomycin AChloroquineCholesterolMacrolidesAutophagosomesAutophagy fluxBafilomycin A1ChloroquineIntracellular cholesterol transportSTX17U18666A

Identifiers

PMID36434621
PMCPMC9701069
OpenAlexW4309961553

What OpenQuestion holds

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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.