Fluorescent Reporters, Imaging, and Artificial Intelligence Toolkits to Monitor and Quantify Autophagy, Heterophagy, and Lysosomal Trafficking Fluxes.
Publisher DOI
PubMed ID
39450581
Abstract
Lysosomal compartments control the clearance of cell-own material (autophagy) or of material that cells endocytose from the external environment (heterophagy) to warrant supply of nutrients, to eliminate macromolecules or parts of organelles present in excess, aged, or containing toxic material. Inherited or sporadic mutations in lysosomal proteins and enzymes may hamper their folding in the endoplasmic reticulum (ER) and their lysosomal transport via the Golgi compartment, resulting in lysosomal dysfunction and storage disorders. Defective cargo delivery to lysosomal compartments is harmful to cells and organs since it causes accumulation of toxic compounds and defective organellar homeostasis. Assessment of resident proteins and cargo fluxes to the lysosomal compartments is crucial for the mechanistic dissection of intracellular transport and catabolic events. It might be combined with high-throughput screenings to identify cellular, chemical, or pharmacological modulators of these events that may find therapeutic use for autophagy-related and lysosomal storage disorders. Here, discuss qualitative, quantitative and chronologic monitoring of autophagic, heterophagic and lysosomal protein trafficking in fixed and live cells, which relies on fluorescent single and tandem reporters used in combination with biochemical, flow cytometry, light and electron microscopy approaches implemented by artificial intelligence-based technology.
Date Issued
2024-10
Publication Type
Article
Subject(s)
Subjects
ER‐phagy
•
ER‐to‐lysosome‐associated degradation (ERLAD)
•
artificial intelligence
•
autophagy
•
autophagy flux
•
endolysosomes (EL)
•
heterophagy
•
lysosomal storage disorders (LSD)
•
lysosomes
•
tandem fluorescent reporters
Language(s)
en
Author(s)
Rudinskiy, Mikhail |
Morone, Diego |
Molinari, Maurizio |
Additional Credits
Journal
Traffic: The moving front of cell biology
Publisher
Wiley
ISSN
1600-0854
1398-9219
Access(Rights)
open.access