Year: 2026
Type: article
Abstract: BECLIN1 is a central regulator of autophagy and endocytic trafficking essential for epithelial homeostasis. While complete intestinal epithelial loss of BECLIN1 causes fatal enteritis, the consequence of its partial loss in the gut remains unclear. Given that BECLIN1 expression can vary in human disease, we investigated whether reduced BECLIN1 is sufficient to impair gut barrier function. Heterozygous Becn1 deletion ( Becn1 +/− ) in the mouse intestinal epithelium caused subtle but functionally important defects, including shortened small intestines, reduced colonic crypt length, altered epithelial architecture, and loss of goblet cells with reduced mucin production, particularly in mature goblet cells. These changes occurred despite preservation of basal autophagy, implicating trafficking-related functions. Supporting this conclusion, Becn1 +/− intestinal epithelial cells showed modest increases in RAB5 + ve vesicles, redistribution of E-CADHERIN with F-actin along lateral membranes, increased apico-basal cell length and reduced basal width. Following dextran sulfate sodium (DSS) treatment, Becn1 +/− mice exhibited greater weight loss, higher disease activity, more severe histological colitis score, and disproportionate loss of neutral mucins, with inflammation confined to the mucosa. Goblet cell dysfunction likely underpinned these barrier defects. These findings establish that BECLIN1 insufficiency destabilises epithelial organisation and barrier defence, thereby sensitising the gut to inflammatory challenge and further positioning BECLIN1 as a key determinant of intestinal homeostasis.
Source: Cell Death and Disease
Authors: Juliani Juliani, Sharon Tran, Tiffany J. Harris, Sarah L. Ellis, Aysha H. Al-Ani, Yashodha Wijebandara, Komal M. Patel, Samuel N. Young, Marco Evangelista, David Baloyan, Camilla M. Reehorst, Rebecca Nightingale, Laura J. Jenkins, Peter De Cruz, Kinga Duszyc, Benjamin T. Kile, Alpha S. Yap, John M. Mariadason, Britt Christensen, André L. Samson, James M. Murphy, Walter D. Fairlie, Erinna F. Lee
Institutions: La Trobe University, Olivia Newton-John Cancer Research Institute, The Royal Melbourne Hospital, The University of Melbourne, Walter and Eliza Hall Institute of Medical Research, Austin Hospital, Austin Health, The University of Queensland, Institute for Molecular Bioscience, Garvan Institute of Medical Research, Monash University, Olivia Newton-John Cancer Wellness & Research Centre
Language: English
Topic: Inflammatory Bowel Disease
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,990
OpenAlex ID: W7165049939