Lysosomal membrane and function

The lysosome is a specialized membrane-bound organelle that serves as the primary degradative compartment of the cell, housing over 60 acidic hydrolases (Settembre et al., 2013, Nature Reviews Molecular Cell Biology). The lysosomal membrane is critical for maintaining an acidic luminal pH (4.5–5.0) through the action of V-ATPases and for regulating the efflux of catabolic products via specific transporters (Appelqvist et al., 2013, Journal of Molecular Cell Biology). Beyond waste disposal, the lysosome acts as a metabolic signaling hub, integrating nutrient sensing through the mTORC1 pathway (Wang et al., 2018, Trends in Cell Biology). Dysregulation of lysosomal function or membrane integrity is a hallmark of lysosomal storage diseases (LSDs), such as Gaucher and Pompe disease, and is increasingly implicated in neurodegenerative disorders like Parkinson's and Alzheimer's (Platt et al., 2018, Nature). Pharmacological interventions include enzyme replacement therapies, substrate reduction agents, and lysosomotropic drugs like hydroxychloroquine that alter luminal pH (Boya & Kroemer, 2008, Nature Reviews Drug Discovery). In oncology, the induction of lysosomal membrane permeabilization (LMP) is explored as a mechanism to bypass apoptosis resistance and trigger cathepsin-mediated cell death (Boya & Kroemer, 2008, Nature Reviews Drug Discovery).

Other names

LysosomeLysosomal compartmentLysosomal membrane permeabilizationLMPLysosomal system

Modulation of lysosomal pH, enzyme replacement therapy (ERT), substrate reduction therapy (SRT), pharmacological chaperoning, or induction of lysosomal membrane permeabilization (LMP).