BORC coordinates encounter and fusion of lysosomes with autophagosomes
Open accessAbstract
Whereas the mechanisms involved in autophagosome formation have been extensively studied for the past 2 decades, those responsible for autophagosome-lysosome fusion have only recently begun to garner attention. In this study, we report that the multisubunit BORC complex, previously implicated in kinesin-dependent movement of lysosomes toward the cell periphery, is required for efficient autophagosome-lysosome fusion. Knockout (KO) of BORC subunits causes not only juxtanuclear clustering of lysosomes, but also increased levels of the autophagy protein LC3B-II and the receptor SQSTM1. Increases in LC3B-II occur without changes in basal MTORC1 activity and autophagy initiation. Instead, LC3B-II accumulation largely results from decreased lysosomal degradation. Further experiments show that BORC KO impairs both the encounter and fusion of autophagosomes with lysosomes. Reduced encounters result from an inability of lysosomes to move toward the peripheral cytoplasm, where many autophagosomes are formed. However, BORC KO also reduces the recruitment of the HOPS tethering complex to lysosomes and assembly of the STX17-VAMP8-SNAP29 trans-SNARE complex involved in autophagosome-lysosome fusion. Through these dual roles, BORC integrates the kinesin-dependent movement of lysosomes toward autophagosomes with HOPS-dependent autophagosome-lysosome fusion. These findings reveal a requirement for lysosome dispersal in autophagy that is independent of changes in MTORC1 signaling, and identify BORC as a novel regulator of autophagosome-lysosome fusion.
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BORC has been implicated in regulating lysosome positioning in concert with amino acid signaling through Ragulator-Rag and also lysosome-autophagosome fusion during autophagy.
“BORC has been implicated in regulating lysosome positioning in concert with amino acid signaling through Ragulator-Rag (Filipek et al., 2017; Pu et al., 2017) and also lysosome-autophagosome fusion during autophagy (Jia et al., 2017)”
From Signal integration in the (m)TORC1 growth pathway (2018) · cites this paper as Jia et al., 2017
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- Authors
- Jia, R., Guardia, C. M., Pu, J., Chen, Y., & Bonifacino, J. S.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Bonifacino, Juan S.
- Venue
- Autophagy
- Publisher
- Informa UK Limited
- Published
- 2017-09-07
- Volume
- 13
- Issue
- 10
- Pages
- 1648-1663
- ISSN
- 1554-8627 (ISSN-L)
- 1554-8635
- PMC
- PMC5640200
- OpenAlex
- W2747494266
- Cited by
- 160
- References
- 51
- Citations by year
- 2026: 13 · 2025: 14 · 2024: 29 · 2023: 16 · 2022: 16 · 2021: 18 · 2020: 23 · 2019: 17 · 2018: 13 · 2017: 1
- FWCI
- 11.56
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Autophagy (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- autophagosome-lysosome fusion, lysosome motility, LC3B-II, p62, mTORC1, lysosomal degradation, autophagy regulation
- MeSH terms
- Autophagosomes, Carrier Proteins, HeLa Cells, Humans, Lysosomes, Membrane Fusion, Nerve Tissue Proteins, Protein Binding, Protein Subunits, Multiprotein Complexes, SNARE Proteins, Protein Multimerization, Gene Knockdown Techniques, HEK293 Cells
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