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Berger 2016 Nat Commun

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Publications in the MiPMap
Berger E, Rath E, Yuan D, Waldschmitt N, Khaloian S, Allgäuer M, Staszewski O, Lobner EM, Schöttl T, Giesbertz P, Coleman OI, Prinz M, Weber A, Gerhard M, Klingenspor M, Janssen KP, Heikenwalder M, Haller D (2016) Mitochondrial function controls intestinal epithelial stemness and proliferation. Nat Commun 7:13171.

» PMID: 27786175 Open Access

Berger E, Rath E, Yuan D, Waldschmitt N, Khaloian S, Allgaeuer M, Staszewski O, Lobner EM, Schoettl T, Giesbertz P, Coleman OI, Prinz M, Weber A*, Gerhard M, Klingenspor M, Janssen KP, Heikenwalder M, Haller D (2016) Nat Commun

Abstract: 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.

Bioblast editor: Kandolf G O2k-Network Lab: DE Freising Klingenspor M


Labels: MiParea: Respiration 


Organism: Mouse  Tissue;cell: Endothelial;epithelial;mesothelial cell 


Coupling state: LEAK, OXPHOS  Pathway: S, ROX  HRR: Oxygraph-2k 

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