Deathly triangle for pancreatic β-cells: Hippo pathway-MTORC1-autophagy

Ardestani, Amin; Maedler, Kathrin

Abstract

A progressive decline in the macroautophagic/autophagic flux is a hallmark of pancreatic β-cell failure in type 2 diabetes (T2D) but the responsible intrinsic factors and underlying molecular mechanisms are incompletely understood. A stress-sensitive multicomponent cellular loop of the Hippo pathway kinase LATS2 (large tumor suppressor 2), MTOR (mechanistic target of rapamycin kinase) complex 1 (MTORC1) and autophagy regulates β-cell survival and metabolic adaptation. Chronic metabolic stress leads to LATS2 hyperactivation which then induces MTORC1, subsequently impairing the cellular autophagic flux and consequently triggering β-cell death. Reciprocally, under physiological conditions, autophagy controls β-cell survival by lysosomal degradation of LATS2. These signaling cross-talks and the interaction between autophagy and LATS2 are important for the regulation of β-cell turnover and functional compensation under metabolic stress.

Citation

Ardestani, A., & Maedler, K. (2021). Deathly triangle for pancreatic β-cells: Hippo pathway-MTORC1-autophagy. Autophagy, 17(12), 4494-4496. https://doi.org/10.1080/15548627.2021.1972404

• Acceptance Date: Aug 20, 2021
• Online Publication Date: Sep 1, 2021
• Publication Date: Jan 1, 2021
• Deposit Date: Jan 4, 2024
• Publicly Available Date: Jan 8, 2024
• Journal: Autophagy
• Print ISSN: 1554-8627
• Electronic ISSN: 1554-8635
• Publisher: Taylor and Francis Group
• Peer Reviewed: Peer Reviewed
• Volume: 17
• Issue: 12
• Pages: 4494-4496
• DOI: https://doi.org/10.1080/15548627.2021.1972404
• Keywords: Autophagy; Beta cells; Diabetes; LATS2; MTORC1; Type 2 diabetes
• Public URL: https://hull-repository.worktribe.com/output/4461581