Signals from the lysosome: a control centre for cellular clearance and energy metabolism

Abstract

Preface For a long time lysosomes were considered merely to be cellular “incinerators” involved in the degradation and recycling of cellular waste. However, there is now compelling evidence indicating that lysosomes have a much broader function and that they are involved in fundamental processes such as secretion, plasma membrane repair, signaling and energy metabolism. Furthermore, the essential role of lysosomes in the autophagic pathway puts these organelles at the crossroads of several cellular processes, with significant implications for health and disease. The identification of a master gene, transcription factor EB (TFEB), that regulates lysosomal biogenesis and autophagy, has revealed how the lysosome adapts to environmental cues, such as starvation, and suggests novel therapeutic strategies for modulating lysosomal function in human disease.

RNASET2 is required for ROS propagation during oxidative stress-mediated cell death

“…32,39,47 Our study provides new insights into the function of this lysosomal enzyme as a regulator of pathophysiological oxidative stress responses and adds to a growing body of evidence that the lysosome and its components are essential for integrating a wide array of metabolic stimuli into cell fate decisions. 48,49 Future studies to establish the precise substrates of RNASET2 will shed important light on the mechanisms through which it functions to control cellular oxidative tone. Cells.…”

Insulin-degrading enzyme secretion from astrocytes is mediated by an autophagy-based unconventional secretory pathway in Alzheimer disease

“…The lysosomal lumen contains approximately 60 different soluble hydrolases, which are active in the acidic environment of the lumen (pH 4.5-5.0). 37 Many lysosomal proteins, such as lysosomal-associated membrane protein 1 (LAMP1) and cathepsins, are protected from lysosomal degradation by post-translational modifications such as mannose-6-phosphate tagging or hyper-glycosylation. Since IDE does not have these modification sites, we investigated mechanisms other than lysosomal degradation.…”

Arf-like GTPase Arl8: Moving from the periphery to the center of lysosomal biology

“…As such, impairment of lysosomal function can manifest in diseased states including cancer, lysosomal storage disorders, and neurodegenerative diseases. [5][6][7][8][9] Lysosome function is also required for various other cellular processes including cholesterol homeostasis, plasma membrane repair, antigen presentation, exosome release, and cell migration. 10 Members of Rab, Arf and Arf-like (Arl) GTPases of the Ras superfamily are key molecular players that associate with distinct intracellular organelles and regulate membrane trafficking to and from these compartments.…”