RRC ID 53358
Author Li Y, Chen B, Zou W, Wang X, Wu Y, Zhao D, Sun Y, Liu Y, Chen L, Miao L, Yang C, Wang X.
Title The lysosomal membrane protein SCAV-3 maintains lysosome integrity and adult longevity.
Journal J Cell Biol
Abstract Lysosomes degrade macromolecules and recycle metabolites as well as being involved in diverse processes that regulate cellular homeostasis. The lysosome is limited by a single phospholipid bilayer that forms a barrier to separate the potent luminal hydrolases from other cellular constituents, thus protecting the latter from unwanted degradation. The mechanisms that maintain lysosomal membrane integrity remain unknown. Here, we identified SCAV-3, the Caenorhabditis elegans homologue of human LIMP-2, as a key regulator of lysosome integrity, motility, and dynamics. Loss of scav-3 caused rupture of lysosome membranes and significantly shortened lifespan. Both of these phenotypes were suppressed by reinforced expression of LMP-1 or LMP-2, the C. elegans LAMPs, indicating that longevity requires maintenance of lysosome integrity. Remarkably, reduction in insulin/insulin-like growth factor 1 (IGF-1) signaling suppressed lysosomal damage and extended the lifespan in scav-3(lf) animals in a DAF-16-dependent manner. Our data reveal that SCAV-3 is essential for preserving lysosomal membrane stability and that modulation of lysosome integrity by the insulin/IGF-1 signaling pathway affects longevity.
Volume 215(2)
Pages 167-185
Published 2016-10-24
DOI 10.1083/jcb.201602090
PII jcb.201602090
PMID 27810910
PMC PMC5084646
MeSH Animals Autophagy Caenorhabditis elegans / cytology Caenorhabditis elegans / physiology* Caenorhabditis elegans / ultrastructure Caenorhabditis elegans Proteins / metabolism* Endoplasmic Reticulum / metabolism Endoplasmic Reticulum / ultrastructure Endosomes / metabolism Endosomes / ultrastructure Glycosylation Golgi Apparatus / metabolism Golgi Apparatus / ultrastructure Green Fluorescent Proteins / metabolism Hydrolases / metabolism Insulin / metabolism Insulin-Like Growth Factor I / metabolism Intracellular Membranes / metabolism Intracellular Membranes / ultrastructure Longevity* Lysosomes / metabolism* Lysosomes / ultrastructure Membrane Proteins / metabolism* Mutation / genetics Protein Stability Signal Transduction
IF 8.891
Times Cited 18
C.elegans tm3659 tm6600