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

JOURNAL OF MOLECULAR BIOLOGY

卷:432

Review

Vivot, Kevin^1,2,3,4  Pasquier, Adrien⁵  Goginashvili, Alexander⁶  Ricci, Romeo^1,2,3,4,7 

[1] Inst Genet & Biol Mol & Cellulaire, F-67404 Illkirch Graffenstaden, France

[2] CNRS, UMR7104, F-67404 Illkirch Graffenstaden, France

[3] INSERM, U964, F-67404 Illkirch Graffenstaden, France

[4] Univ Strasbourg, F-67081 Strasbourg, France

[5] Telethon Inst Genet & Med TIGEM, Pozzuoli, Italy

[6] Univ Calif San Diego, Dept Cellular & Mol Med, Ludwig Inst Canc Res, La Jolla, CA 92093 USA

[7] Nouvel Hop Civil, Lab Biochim & Biol Mol, F-67091 Strasbourg, France

关键词: Diabetes;    Lysosome;    Autophagy;    Crinophagy;    Nutrient signaling;   

DOI  :  10.1016/j.jmb.2019.07.030

来源: Elsevier

【 摘 要 】

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. (C) 2019 Elsevier Ltd. All rights reserved.

【 授权许可】

Free