Lysosomal membrane and acidic organelle components

Lysosomal membrane and acidic organelle components refer to the structural and functional elements of the lysosome and related acidic compartments that serve as therapeutic targets. These components include the vacuolar-type H+-ATPase (V-ATPase) proton pump, which maintains an acidic luminal pH (4.5–5.0), and various membrane proteins like LAMP1 and LAMP2 that maintain organelle integrity. Drugs targeting these components, such as the lysosomotropic weak bases chloroquine and hydroxychloroquine, accumulate within the acidic lumen through ion trapping, leading to an increase in pH and the subsequent inhibition of acid hydrolases. This disruption impairs critical cellular processes such as autophagy, antigen processing, and heme detoxification in parasites like Plasmodium falciparum. In cancer therapy, inducing lysosomal membrane permeabilization (LMP) is an emerging strategy to trigger lysosome-dependent cell death by releasing proteolytic cathepsins into the cytosol. However, the sequestration of basic drugs within these organelles can also contribute to multidrug resistance by reducing the concentration of drugs at their primary cytoplasmic or nuclear targets.

Other names

LysosomeAcidic organellesLysosomal membraneEndolysosomal system

Lysosomotropic accumulation (ion trapping), elevation of intralysosomal pH, inhibition of lysosomal enzymes (acid hydrolases), and induction of lysosomal membrane permeabilization (LMP).