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BECLIN1 is essential for intestinal homeostasis involving autophagy-independent mechanisms through its function in endocytic trafficking.
Tran, Sharon; Juliani, Juliani; Harris, Tiffany J; Evangelista, Marco; Ratcliffe, Julian; Ellis, Sarah L; Baloyan, David; Reehorst, Camilla M; Nightingale, Rebecca; Luk, Ian Y; Jenkins, Laura J; Ghilas, Sonia; Yakou, Marina H; Inguanti, Chantelle; Johnson, Chad; Buchert, Michael; Lee, James C; De Cruz, Peter; Duszyc, Kinga; Gleeson, Paul A; Kile, Benjamin T; Mielke, Lisa A; Yap, Alpha S; Mariadason, John M; Fairlie, W Douglas; Lee, Erinna F.
Afiliación
  • Tran S; Olivia Newton-John Cancer Research Institute, Heidelberg, VIC, Australia.
  • Juliani J; School of Cancer Medicine, La Trobe University, Bundoora, VIC, Australia.
  • Harris TJ; Olivia Newton-John Cancer Research Institute, Heidelberg, VIC, Australia.
  • Evangelista M; School of Cancer Medicine, La Trobe University, Bundoora, VIC, Australia.
  • Ratcliffe J; Department of Biochemistry and Chemistry, School of Agriculture, Biomedicine and Environment, La Trobe University, Bundoora, VIC, Australia.
  • Ellis SL; La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, Australia.
  • Baloyan D; Olivia Newton-John Cancer Research Institute, Heidelberg, VIC, Australia.
  • Reehorst CM; School of Cancer Medicine, La Trobe University, Bundoora, VIC, Australia.
  • Nightingale R; Olivia Newton-John Cancer Research Institute, Heidelberg, VIC, Australia.
  • Luk IY; School of Cancer Medicine, La Trobe University, Bundoora, VIC, Australia.
  • Jenkins LJ; Bioimaging Platform, La Trobe University, Bundoora, VIC, Australia.
  • Ghilas S; Olivia Newton-John Cancer Research Institute, Heidelberg, VIC, Australia.
  • Yakou MH; School of Cancer Medicine, La Trobe University, Bundoora, VIC, Australia.
  • Inguanti C; Olivia Newton-John Cancer Research Institute, Heidelberg, VIC, Australia.
  • Johnson C; School of Cancer Medicine, La Trobe University, Bundoora, VIC, Australia.
  • Buchert M; Olivia Newton-John Cancer Research Institute, Heidelberg, VIC, Australia.
  • Lee JC; School of Cancer Medicine, La Trobe University, Bundoora, VIC, Australia.
  • De Cruz P; Olivia Newton-John Cancer Research Institute, Heidelberg, VIC, Australia.
  • Duszyc K; School of Cancer Medicine, La Trobe University, Bundoora, VIC, Australia.
  • Gleeson PA; Olivia Newton-John Cancer Research Institute, Heidelberg, VIC, Australia.
  • Kile BT; School of Cancer Medicine, La Trobe University, Bundoora, VIC, Australia.
  • Mielke LA; Olivia Newton-John Cancer Research Institute, Heidelberg, VIC, Australia.
  • Yap AS; School of Cancer Medicine, La Trobe University, Bundoora, VIC, Australia.
  • Mariadason JM; Olivia Newton-John Cancer Research Institute, Heidelberg, VIC, Australia.
  • Fairlie WD; School of Cancer Medicine, La Trobe University, Bundoora, VIC, Australia.
  • Lee EF; Olivia Newton-John Cancer Research Institute, Heidelberg, VIC, Australia.
Commun Biol ; 7(1): 209, 2024 Feb 20.
Article en En | MEDLINE | ID: mdl-38378743
ABSTRACT
Autophagy-related genes have been closely associated with intestinal homeostasis. BECLIN1 is a component of Class III phosphatidylinositol 3-kinase complexes that orchestrate autophagy initiation and endocytic trafficking. Here we show intestinal epithelium-specific BECLIN1 deletion in adult mice leads to rapid fatal enteritis with compromised gut barrier integrity, highlighting its intrinsic critical role in gut maintenance. BECLIN1-deficient intestinal epithelial cells exhibit extensive apoptosis, impaired autophagy, and stressed endoplasmic reticulum and mitochondria. Remaining absorptive enterocytes and secretory cells display morphological abnormalities. Deletion of the autophagy regulator, ATG7, fails to elicit similar effects, suggesting additional novel autophagy-independent functions of BECLIN1 distinct from ATG7. Indeed, organoids derived from BECLIN1 KO mice show E-CADHERIN mislocalisation associated with abnormalities in the endocytic trafficking pathway. This provides a mechanism linking endocytic trafficking mediated by BECLIN1 and loss of intestinal barrier integrity. Our findings establish an indispensable role of BECLIN1 in maintaining mammalian intestinal homeostasis and uncover its involvement in endocytic trafficking in this process. Hence, this study has important implications for our understanding of intestinal pathophysiology.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Apoptosis / Células Epiteliales Límite: Animals Idioma: En Revista: Commun Biol Año: 2024 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Apoptosis / Células Epiteliales Límite: Animals Idioma: En Revista: Commun Biol Año: 2024 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Reino Unido