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Journal Articles Journal of Molecular Biology Year : 2020

Breaking Bad and Breaking Good: beta-Cell Autophagy Pathways in Diabetes


For many decades the lysosome has been recognized as the terminal center of cellular waste disposal. Products of lysosomal degradation are either recycled in biosynthetic pathways or are further metabolized to produce energy. As such the lysosome was attributed a rather passive role in cellular metabolism merely transforming bulk material into small metabolites. More recently, however, the emerging evidence has brought the lysosome to the center of nutrient sensing as the organelle that harbors a complex signaling machinery which dynamically and actively regulates cell metabolism. The pancreatic beta cell is unique in as much as nutrient sensing is directly coupled to insulin secretion. Importantly, defects in insulin secretion constitute a hallmark in the progression of patients from a state of impaired glucose tolerance to full blown type 2 diabetes (T2D). However, mechanisms linking nutrient-dependent lysosomal function to insulin secretion and more generally to beta cell health have evolved only very recently. This review discusses emerging concepts in macroautophagy and macroautophagy-independent processes of cargo delivery to lysosomes as well as nutrient-dependent lysosomal signaling specifically in the context of beta cell function in health and disease. Such mechanisms may provide a novel source of therapeutic targets to be exploited in the context of beta cell failure in diabetes in the near future.

Dates and versions

hal-03664352 , version 1 (10-05-2022)



Kevin Vivot, Adrien Pasquier, Alexander Goginashvili, Romeo Ricci. Breaking Bad and Breaking Good: beta-Cell Autophagy Pathways in Diabetes. Journal of Molecular Biology, 2020, 432 (5), pp.1494-1513. ⟨10.1016/j.jmb.2019.07.030⟩. ⟨hal-03664352⟩
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