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Autophagy. 2020 Feb;16(2):195-202. doi: 10.1080/15548627.2019.1704119. Epub 2019 Dec 23.

Autophagy modulator scoring system: a user-friendly tool for quantitative analysis of methodological integrity of chemical autophagy modulator studies.

Author information

1
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, SAR China.
2
Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
3
Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ, USA.
4
School of Pharmaceutical Sciences, National and Local United Engineering Lab of Druggability and New Drugs Evaluation, Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, Sun Yat-Sen University, Guangzhou, Guangdong, China.
5
Key Laboratory of Protein Modification and Degradation, State Key Laboratory of Respiratory Disease, College of Basic Medical Science, Guangzhou Medical University, Guangdong, China.
6
Medical College of Acupuncture-Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.
7
Mr. & Mrs. Ko Chi-Ming Centre for Parkinson's Disease Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, SAR China.
8
Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy.
9
Medical Genetics Unit, Department of Medical and Translational Science, Federico II University, Naples, Italy.
10
Center for medical genetics, Central South University, Changsha, Hunan, China.
11
Institute of Molecular Precision Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China.
12
Departments of Neurology and Neuroscience, Friedman Brain Institute, Mount Sinai School of Medicine, New York, NY, USA.

Abstract

Over the past 20 years (1999-2019), we have witnessed a rapid increase in publications involving chemical macroautophagy/autophagy modulators. However, an overview of the methodologies used in these studies is still lacking, and methodology flaws are frequently observed in some reports. To provide an objective and quantitative analysis of studies involving autophagy modulators, we present an Autophagy Modulator Scoring System (AMSS), which is designed to evaluate methodological integrity. AMSS-A includes the autophagy characterization by 4 aspects, namely, autophagosome quantification, autophagy-related biochemical changes, autophagy substrate degradation, and autophagic flux. AMSS-B contains the pharmacological and functional characteristics of chemical autophagy modulators, including lysosomal function, drug targets, autophagy-dependent pharmacological effects, and validation in multiple cell lines and in vivo models. Our analysis shows that of the 385 studies reporting chemical autophagy modulators, only 142 single studies had examined all 4 aspects of autophagy characterization in AMSS-A, and only 10 out of 142 studies had fulfilled all the AMSS criteria in a single study. A comprehensive analysis of the methodologies used in all the studies was made, along with a summary of studies that demonstrated the highest methodological integrity based on AMSS ranking. To test the reliability of the AMSS, a co-efficiency analysis of scores and co-citation values in the co-citation network was performed, and a significant co-efficiency was obtained. Collectively, AMSS provides insight into the methodological integrity of autophagy modulators studies and also offers a user-friendly toolkit to help choose appropriate assays to characterize autophagy modulators.Abbreviations: 3-MA: 3-methyladenine; AMSS: Autophagy Modulator Scoring System; ATG: autophagy-related; BAF: bafilomycin A1; BECN1: beclin 1; CQ: chloroquine; GFP: green fluorescent protein; LC3: microtubule associated protein 1 light chain 3; mRFP: monomeric red fluorescent protein; MTOR: mechanistic target of rapamycin kinase; PtdIns3K: phosphatidylinositol 3-kinase; PtdIns3P: phosphatidylinositol-3-phosphate.

KEYWORDS:

Autophagy modulator; autophagy modulator scoring system; autophagy-monitoring methods; co-citation network; methodology

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