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Lysosome heterogeneity and diversity mapped through its distinct cellular functions

Indira Chavan, Arindam Bhattacharjee

2025Cellular and Molecular Life Sciences8 citationsDOIOpen Access PDF

Abstract

Lysosomes respond to cellular nutrient availability and diverse oncoming vesicle traffic such as endocytosis and autophagy by switching between anabolic signaling or catabolic hydrolase activity, which coincides with a drastic shift in their cellular distribution, organelle contacts, ion homeostasis, membrane proteome and lipidome. Emerging evidence now reveals a dynamic remodeling of lysosomal membrane to counter membrane damage, acting via extensive lipid transfer from the endoplasmic reticulum or by localized membrane repair. Functionally, lysosomes play a key role in lipid metabolism and intracellular calcium signaling. Unsurprisingly, disease-associated lysosomes are either often hyperactive- thus promoting abnormal tissue growth, or hypoactive, promoting storage. Taken together, this presents an incredible functional diversity among the cellular population of lysosomes. Here, we discuss this intracellular heterogeneity and intercellular diversity in context of lysosomal function in health and disease.

Topics & Concepts

Cell biologyLysosomeBiologyEndocytosisEndoplasmic reticulumIntracellularAutophagyContext (archaeology)Membrane contact siteEndocytic cycleOrganellePopulationOrganelle biogenesisCellular compartmentCalcium signalingAnabolismBiogenesisFunction (biology)VesicleLipid dropletExocytosisCell signalingMitophagyLipid metabolismMembrane transportCatabolismGolgi apparatusRabMitochondrionEndosomeTransmembrane proteinLipid microdomainCytosolTransport proteinMannose 6-phosphate receptorLysosomal storage diseaseCell physiologyBiochemistryAutophagy in Disease and TherapyCalcium signaling and nucleotide metabolismLysosomal Storage Disorders Research
Lysosome heterogeneity and diversity mapped through its distinct cellular functions | Litcius