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Mitochondrial function controls intestinal epithelial stemness and proliferation.
Berger, Emanuel; Rath, Eva; Yuan, Detian; Waldschmitt, Nadine; Khaloian, Sevana; Allgäuer, Michael; Staszewski, Ori; Lobner, Elena M; Schöttl, Theresa; Giesbertz, Pieter; Coleman, Olivia I; Prinz, Marco; Weber, Achim; Gerhard, Markus; Klingenspor, Martin; Janssen, Klaus-Peter; Heikenwalder, Mathias; Haller, Dirk.
Afiliação
  • Berger E; Technische Universität München, Chair of Nutrition and Immunology, 85350 Freising-Weihenstephan, Germany.
  • Rath E; Technische Universität München, Chair of Nutrition and Immunology, 85350 Freising-Weihenstephan, Germany.
  • Yuan D; Helmholtz-Zentrum München, Institute of Virology, 85764 Neuherberg, Germany.
  • Waldschmitt N; Technische Universität München, Chair of Nutrition and Immunology, 85350 Freising-Weihenstephan, Germany.
  • Khaloian S; Technische Universität München, Chair of Nutrition and Immunology, 85350 Freising-Weihenstephan, Germany.
  • Allgäuer M; Technische Universität München, Institute of Medical Microbiology, Immunology and Hygiene, 81675 Munich, Germany.
  • Staszewski O; University of Freiburg, Institute of Neuropathology, Freiburg 79106, Germany.
  • Lobner EM; Technische Universität München, Chair of Nutrition and Immunology, 85350 Freising-Weihenstephan, Germany.
  • Schöttl T; Technische Universität München, Chair of Molecular Nutritional Medicine, Else Kröner-Fresenius Center, 85350 Freising-Weihenstephan, Germany.
  • Giesbertz P; Technische Universität München, Department of Nutritional Physiology, 85350 Freising-Weihenstephan, Germany.
  • Coleman OI; Technische Universität München, Chair of Nutrition and Immunology, 85350 Freising-Weihenstephan, Germany.
  • Prinz M; University of Freiburg, Institute of Neuropathology, Freiburg 79106, Germany.
  • Weber A; BIOSS Centre for Biological Signalling Studies, University of Freiburg, 79104 Freiburg, Germany.
  • Gerhard M; University Hospital Zurich, Institute of Surgical Pathology, 8091 Zurich, Switzerland.
  • Klingenspor M; Technische Universität München, Institute of Medical Microbiology, Immunology and Hygiene, 81675 Munich, Germany.
  • Janssen KP; Technische Universität München, Chair of Molecular Nutritional Medicine, Else Kröner-Fresenius Center, 85350 Freising-Weihenstephan, Germany.
  • Heikenwalder M; Technische Universität München, ZIEL-Institute for Food &Health, 85350 Freising-Weihenstephan, Germany.
  • Haller D; Technische Universität München, Department of Surgery, 81675 Munich, Germany.
Nat Commun ; 7: 13171, 2016 10 27.
Article em En | MEDLINE | ID: mdl-27786175
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proliferação de Células / Células-Tronco Embrionárias / Mucosa Intestinal / Mitocôndrias Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Alemanha

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proliferação de Células / Células-Tronco Embrionárias / Mucosa Intestinal / Mitocôndrias Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Alemanha