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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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
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
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
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Virology (VIRO)