Biogenesis of lysosome-related organelles complex-1 (BORC) regulates late endosomal/lysosomal size through PIKfyve-dependent phosphatidylinositol-3,5-bisphosphate.

Autor: Yordanov TE; Division of Cell Biology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria., Hipolito VEB; Department of Chemistry and Biology and the Graduate Program in Molecular Science, Ryerson University, Toronto, Ontario, Canada., Liebscher G; Division of Cell Biology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria., Vogel GF; Division of Cell Biology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria.; Department of Pediatrics I, Medical University of Innsbruck, Innsbruck, Austria., Stasyk T; Division of Cell Biology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria., Herrmann C; Division of Cell Biology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria., Geley S; Division of Molecular Pathophysiology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria., Teis D; Division of Cell Biology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria., Botelho RJ; Department of Chemistry and Biology and the Graduate Program in Molecular Science, Ryerson University, Toronto, Ontario, Canada., Hess MW; Division of Histology and Embryology, Medical University of Innsbruck, Innsbruck, Austria., Huber LA; Division of Cell Biology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria.; Austrian Drug Screening Institute, ADSI, Innsbruck, Austria.
Jazyk: angličtina
Zdroj: Traffic (Copenhagen, Denmark) [Traffic] 2019 Sep; Vol. 20 (9), pp. 674-696.
DOI: 10.1111/tra.12679
Abstrakt: Mechanisms that control lysosomal function are essential for cellular homeostasis. Lysosomes adapt in size and number to cellular needs but little is known about the underlying molecular mechanism. We demonstrate that the late endosomal/lysosomal multimeric BLOC-1-related complex (BORC) regulates the size of these organelles via PIKfyve-dependent phosphatidylinositol-3,5-bisphosphate [PI(3,5)P 2 ] production. Deletion of the core BORC component Diaskedin led to increased levels of PI(3,5)P 2 , suggesting activation of PIKfyve, and resulted in enhanced lysosomal reformation and subsequent reduction in lysosomal size. This process required AMP-activated protein kinase (AMPK), a known PIKfyve activator, and was additionally dependent on the late endosomal/lysosomal adaptor, mitogen-activated protein kinases and mechanistic target of rapamycin activator (LAMTOR/Ragulator) complex. Consistently, in response to glucose limitation, AMPK activated PIKfyve, which induced lysosomal reformation with increased baseline autophagy and was coupled to a decrease in lysosomal size. These adaptations of the late endosomal/lysosomal system reversed under glucose replete growth conditions. In summary, our results demonstrate that BORC regulates lysosomal reformation and size in response to glucose availability.
(© 2019 The Authors. Traffic published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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