Evidence map›Paper›PMID 37252359›Full record

ArticleACS central science2023

A Turn-On Fluorescent Amino Acid Sensor Reveals Chloroquine's Effect on Cellular Amino Acids via Inhibiting Cathepsin L.

Michael R Smith, Le Zhang, Yizhen Jin, Min Yang, Anusha Bade, Kevin D Gillis, Sadhan Jana, Ramesh Naidu Bypaneni, Timothy E Glass, Hening Lin

Open access · diamondAbstract read
In one paragraph

Article in ACS central science, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
4.7field-weighted citation impact, top 4% 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

7 citing papers in PubMed, 22 citations in OpenAlex.

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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

10 authors at 3 institutions in 1 country.

Michael R SmithDepartment of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, United States.
Le ZhangDepartment of Chemistry, University of Missouri, Columbia, Missouri 65211, United States.
Yizhen JinGraduate Program of Biochemistry, Molecular and Cell Biology, Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, United States.
Min YangDepartment of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, United States.
Anusha BadeDepartment of Chemistry, University of Missouri, Columbia, Missouri 65211, United States.
Kevin D GillisDalton Cardiovascular Research Center, Department of Bioengineering and Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, Missouri 65211, United States.
Sadhan JanaDepartment of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, United States.
Ramesh Naidu BypaneniDepartment of Chemistry, University of Missouri, Columbia, Missouri 65211, United States.
Timothy E GlassDepartment of Chemistry, University of Missouri, Columbia, Missouri 65211, United States.ORCID https://orcid.org/0000-0002-5064-3341
Hening LinDepartment of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, United States.ORCID https://orcid.org/0000-0002-0255-2701
University of Missouri · USCornell University · USHoward Hughes Medical Institute · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Maintaining homeostasis of metabolites such as amino acids is critical for cell survival. Dysfunction of nutrient balance can result in human diseases such as diabetes. Much remains to be discovered about how cells transport, store, and utilize amino acids due to limited research tools. Here we developed a novel, pan-amino acid fluorescent turn-on sensor, NS560. It detects 18 of the 20 proteogenic amino acids and can be visualized in mammalian cells. Using NS560, we identified amino acids pools in lysosomes, late endosomes, and surrounding the rough endoplasmic reticulum. Interestingly, we observed amino acid accumulation in large cellular foci after treatment with chloroquine, but not with other autophagy inhibitors. Using a biotinylated photo-cross-linking chloroquine analog and chemical proteomics, we identified Cathepsin L (CTSL) as the chloroquine target leading to the amino acid accumulation phenotype. This study establishes NS560 as a useful tool to study amino acid regulation, identifies new mechanisms of action of chloroquine, and demonstrates the importance of CTSL regulation of lysosomes.

Identifiers

PMID37252359
PMCPMC10214525
OpenAlexW4366815953

What OpenQuestion holds

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LicenceCC BY
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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.