Selective Lysosomal Transporter Degradation by Organelle Membrane Fusion
- PMID: 28017618
- DOI: 10.1016/j.devcel.2016.11.024
Selective Lysosomal Transporter Degradation by Organelle Membrane Fusion
Abstract
Lysosomes rely on their resident transporter proteins to return products of catabolism to the cell for reuse and for cellular signaling, metal storage, and maintaining the lumenal environment. Despite their importance, little is known about the lifetime of these transporters or how they are regulated. Using Saccharomyces cerevisiae as a model, we discovered a new pathway intrinsic to homotypic lysosome membrane fusion that is responsible for their degradation. Transporter proteins are selectively sorted by the docking machinery into an area between apposing lysosome membranes, which is internalized and degraded by lumenal hydrolases upon organelle fusion. These proteins have diverse lifetimes that are regulated in response to protein misfolding, changing substrate levels, or TOR activation. Analogous to endocytosis for controlling surface protein levels, the "intralumenal fragment pathway" is critical for lysosome membrane remodeling required for organelle function in the context of cellular protein quality control, ion homeostasis, and metabolism.
Keywords: TOR; intralumenal fragment; lysosomal transporter; lysosome biology; membrane fusion; multivesicular body; protein degradation; protein quality control; vacuole.
Copyright © 2017 Elsevier Inc. All rights reserved.
Similar articles
-
How and why intralumenal membrane fragments form during vacuolar lysosome fusion.Mol Biol Cell. 2017 Jan 15;28(2):309-321. doi: 10.1091/mbc.E15-11-0759. Epub 2016 Nov 23. Mol Biol Cell. 2017. PMID: 27881666 Free PMC article.
-
Ubiquitin-dependent lysosomal membrane protein sorting and degradation.Mol Cell. 2015 Feb 5;57(3):467-78. doi: 10.1016/j.molcel.2014.12.012. Epub 2015 Jan 22. Mol Cell. 2015. PMID: 25620559
-
The intralumenal fragment pathway mediates ESCRT-independent surface transporter down-regulation.Nat Commun. 2018 Dec 18;9(1):5358. doi: 10.1038/s41467-018-07734-5. Nat Commun. 2018. PMID: 30560896 Free PMC article.
-
V-ATPase, ScNhx1p and yeast vacuole fusion.J Genet Genomics. 2012 Apr 20;39(4):167-71. doi: 10.1016/j.jgg.2012.02.001. Epub 2012 Feb 10. J Genet Genomics. 2012. PMID: 22546538 Review.
-
The ubiquitin code of yeast permease trafficking.Trends Cell Biol. 2010 Apr;20(4):196-204. doi: 10.1016/j.tcb.2010.01.004. Trends Cell Biol. 2010. PMID: 20138522 Review.
Cited by
-
SNARE-mediated membrane fusion arrests at pore expansion to regulate the volume of an organelle.EMBO J. 2018 Oct 1;37(19):e99193. doi: 10.15252/embj.201899193. Epub 2018 Aug 17. EMBO J. 2018. PMID: 30120144 Free PMC article.
-
ESCRT, not intralumenal fragments, sorts ubiquitinated vacuole membrane proteins for degradation.J Cell Biol. 2021 Aug 2;220(8):e202012104. doi: 10.1083/jcb.202012104. Epub 2021 May 28. J Cell Biol. 2021. PMID: 34047770 Free PMC article.
-
Lipid Rafts, Sphingolipids, and Ergosterol in Yeast Vacuole Fusion and Maturation.Front Cell Dev Biol. 2020 Jul 3;8:539. doi: 10.3389/fcell.2020.00539. eCollection 2020. Front Cell Dev Biol. 2020. PMID: 32719794 Free PMC article. Review.
-
How and why intralumenal membrane fragments form during vacuolar lysosome fusion.Mol Biol Cell. 2017 Jan 15;28(2):309-321. doi: 10.1091/mbc.E15-11-0759. Epub 2016 Nov 23. Mol Biol Cell. 2017. PMID: 27881666 Free PMC article.
-
TORC1 regulates vacuole membrane composition through ubiquitin- and ESCRT-dependent microautophagy.J Cell Biol. 2020 Mar 2;219(3):e201902127. doi: 10.1083/jcb.201902127. J Cell Biol. 2020. PMID: 32045480 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases