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Mammalian hybrid pre-autophagosomal structure HyPAS generates autophagosomes
Suresh Kumar1, Ruheena Javed1, Michal Mudd1
1Autophagy Inflammation and Metabolism Center, University of New Mexico Health Sciences Center, Albuquerque, NM, USA; Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
Cell
|November 6, 2021
Summary
Autophagosome biogenesis involves a novel hybrid membrane compartment, HyPAS, formed from Golgi and endosomal pathways. This process is targeted by SARS-CoV-2 proteins, impacting autophagosome formation.
Area of Science:
- Cell Biology
- Molecular Biology
- Autophagy Research
Background:
- The precise mechanisms governing mammalian autophagosome biogenesis are not fully elucidated.
- Understanding autophagosome origins is crucial for cellular health and disease research.
Purpose of the Study:
- To define the origin and biogenesis of mammalian autophagosomes.
- To identify novel membrane compartments involved in autophagosome formation.
- To investigate the impact of viral factors on autophagosome precursor assembly.
Main Methods:
- Utilized cellular and in vitro membrane fusion assays.
- Investigated the role of FIP200 vesicles and ATG16L1 membranes.
- Analyzed the effect of SARS-CoV-2 infection and nsp6 expression.
Main Results:
- Identified a hybrid pre-autophagosomal structure (HyPAS) formed by the fusion of cis-Golgi-derived FIP200 vesicles and endosomally derived ATG16L1 membranes.
- Discovered a novel apparatus controlling HyPAS biogenesis and autophagosomal precursor membranes.
- Demonstrated that HyPAS formation is inhibited by SARS-CoV-2 infection and nsp6 expression.
- Showed HyPAS can be modulated by pharmacological agents.
Conclusions:
- Mammalian autophagosome membranes originate from a hybrid compartment (HyPAS) integrating secretory and endosomal pathways.
- Autophagosome biogenesis is a target for microbial factors, exemplified by coronaviral proteins.
- This discovery provides new insights into the regulation of autophagy and its manipulation by viruses.
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