TY - JOUR
T1 - Triggered recruitment of ESCRT machinery promotes endolysosomal repair
AU - Skowyra, Michael L.
AU - Schlesinger, Paul H.
AU - Naismith, Teresa V.
AU - Hanson, Phyllis I.
N1 - Funding Information:
We thank C. Weihl and J. Philips for insightful discussions, reagents, and sharing unpublished data; K. Blumer, D. Kast, and D. Piston for helpful discussions; R. Roth for making deep-etch electron microscopy replicas; A. Ustione for microscopy assistance; and A. Clippinger and members of the Hanson laboratory for helpful discussions, reagents, microscopy assistance, and contributions to experimental design. Funding: This work was supported by R01 GM122434 from the National Institutes of Health (to P.I.H.). Imaging was performed in part through use of the Washington University Center for Cellular Imaging, partially supported by the Children's Discovery Institute at Washington University (CDI-CORE-2015-505). Author contributions: M.L.S., P.H.S., and P.I.H. designed research. All authors performed research and/or analyzed data. M.L.S. and P.I.H. wrote the manuscript. All authors discussed results and commented on the manuscript. Competing interests: The authors declare no competing financial interests. Data and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or the supplementary materials.
Publisher Copyright:
© 2018 American Association for the Advancement of Science. All Rights Reserved.
PY - 2018
Y1 - 2018
N2 - Endolysosomes can be damaged by diverse materials. Terminally damaged compartments are degraded by lysophagy, but pathways that repair salvageable organelles are poorly understood. Here we found that the endosomal sorting complex required for transport (ESCRT) machinery, known to mediate budding and fission on endolysosomes, also plays an essential role in their repair. ESCRTs were rapidly recruited to acutely injured endolysosomes through a pathway requiring calcium and ESCRT-activating factors that was independent of lysophagy. We used live-cell imaging to demonstrate that ESCRTs responded to small perforations in endolysosomal membranes and enabled compartments to recover from limited damage. Silica crystals that disrupted endolysosomes also triggered ESCRT recruitment. ESCRTs thus provide a defense against endolysosomal damage likely to be relevant in physiological and pathological contexts.
AB - Endolysosomes can be damaged by diverse materials. Terminally damaged compartments are degraded by lysophagy, but pathways that repair salvageable organelles are poorly understood. Here we found that the endosomal sorting complex required for transport (ESCRT) machinery, known to mediate budding and fission on endolysosomes, also plays an essential role in their repair. ESCRTs were rapidly recruited to acutely injured endolysosomes through a pathway requiring calcium and ESCRT-activating factors that was independent of lysophagy. We used live-cell imaging to demonstrate that ESCRTs responded to small perforations in endolysosomal membranes and enabled compartments to recover from limited damage. Silica crystals that disrupted endolysosomes also triggered ESCRT recruitment. ESCRTs thus provide a defense against endolysosomal damage likely to be relevant in physiological and pathological contexts.
UR - http://www.scopus.com/inward/record.url?scp=85044993895&partnerID=8YFLogxK
U2 - 10.1126/science.aar5078
DO - 10.1126/science.aar5078
M3 - Article
C2 - 29622626
AN - SCOPUS:85044993895
SN - 0036-8075
VL - 360
JO - Science
JF - Science
IS - 6384
M1 - eaar5078
ER -