Lysosomal acidic compartment

The lysosomal acidic compartment is a specialized membrane-bound organelle characterized by an internal pH of approximately 4.5 to 5.0, maintained by the vacuolar H+-ATPase (V-ATPase) proton pump [1]. This acidic environment is essential for the optimal activity of over 60 different acid hydrolases responsible for the degradation of proteins, lipids, and complex carbohydrates [2]. Beyond its role in waste disposal, the lysosome serves as a metabolic signaling hub, regulating autophagy and nutrient sensing through the recruitment of the mTORC1 complex [1]. In various diseases, such as cancer, the lysosomal compartment is often reorganized or enlarged to support increased metabolic demands, making it a vulnerable target for lysosomotropic drugs that can trigger lysosomal membrane permeabilization and subsequent cell death [4]. Pharmacologically, this compartment is targeted by weakly basic drugs, such as chloroquine and hydroxychloroquine, which accumulate within the lumen via "pH trapping" to neutralize the acidity or inhibit specific lysosomal functions [2]. This sequestration can interfere with viral entry, parasite survival (e.g., Plasmodium in malaria), and autophagic flux in tumor cells [3, 4].

Other names

LysosomeAcidic vacuoleLysosomal lumenAcidic organelle

Lysosomotropism (pH trapping), pH neutralization, inhibition of acid hydrolases, disruption of autophagic flux, lysosomal membrane permeabilization (LMP)