PuSH - Publikationsserver des Helmholtz Zentrums München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
Berger, E.* ; Rath, E.* ; Yuan, D.T. ; Waldschmitt, N.* ; Khaloian, S.* ; Allgäuer, M.* ; Staszewski, O.* ; Lobner, E.M.* ; Schöttl, T.* ; Giesbertz, P.* ; Coleman, O.I.* ; Prinz, M.* ; Weber, A.* ; Gerhard, M.* ; Klingenspor, M.* ; Janssen, K.P.* ; Heikenwälder, M. ; Haller, D.*

Mitochondrial function controls intestinal epithelial stemness and proliferation.

Nat. Commun. 7:13171 (2016)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Control of intestinal epithelial stemness is crucial for tissue homeostasis. Disturbances in epithelial function are implicated in inflammatory and neoplastic diseases of the gastrointestinal tract. Here we report that mitochondrial function plays a critical role in maintaining intestinal stemness and homeostasis. Using intestinal epithelial cell (IEC)-specific mouse models, we show that loss of HSP60, a mitochondrial chaperone, activates the mitochondrial unfolded protein response (MT-UPR) and results in mitochondrial dysfunction. HSP60-deficient crypts display loss of stemness and cell proliferation, accompanied by epithelial release of WNT10A and RSPO1. Sporadic failure of Cre-mediated Hsp60 deletion gives rise to hyperproliferative crypt foci originating from OLFM4(+) stem cells. These effects are independent of the MT-UPR-associated transcription factor CHOP. In conclusion, compensatory hyperproliferation of HSP60(+) escaper stem cells suggests paracrine release of WNT-related factors from HSP60-deficient, functionally impaired IEC to be pivotal in the control of the proliferative capacity of the stem cell niche.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
11.329
2.922
84
91
Tags
Anmerkungen
Besondere Publikation
Auf Hompepage verbergern

Zusatzinfos bearbeiten
Eigene Tags bearbeiten
Privat
Eigene Anmerkung bearbeiten
Privat
Auf Publikationslisten für
Homepage nicht anzeigen
Als besondere Publikation
markieren
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Unfolded Protein Response; Inflammatory-bowel-disease; Hereditary Spastic Paraplegia; Endoplasmic-reticulum Stress; Er-stress; Ulcerative-colitis; Paneth Cells; Susceptibility Loci; Colorectal-cancer; Gene-expression
Sprache
Veröffentlichungsjahr 2016
HGF-Berichtsjahr 2016
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Zeitschrift Nature Communications
Quellenangaben Band: 7, Heft: , Seiten: , Artikelnummer: 13171 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Virology (VIRO)
POF Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Forschungsfeld(er) Immune Response and Infection
PSP-Element(e) G-551600-001
PubMed ID 27786175
DOI 10.1038/ncomms13171
WOS ID WOS:000386308700001
Scopus ID 84993179633
Erfassungsdatum 2016-10-31
[➜Korrektur melden]