Lysosomal and endosomal acidic compartments

Lysosomal and endosomal acidic compartments represent a critical organelle system responsible for the degradation and recycling of cellular materials through the endocytic and autophagic pathways [1]. These compartments maintain a highly acidic internal environment (pH 4.5–6.5) via the activity of vacuolar H+-ATPase (V-ATPase) proton pumps, which is essential for the optimal function of resident acid hydrolases like cathepsins [2]. In oncology, cancer cells often exploit lysosomal biogenesis and acidified compartments to promote nutrient scavenging and resist apoptosis, making them a target for lysosomal membrane permeabilization (LMP) strategies [3]. Furthermore, many viruses, including influenza and coronaviruses, utilize the low pH of endosomes to trigger conformational changes in viral proteins required for membrane fusion and cytosolic entry [4]. Pharmacological intervention typically involves lysosomotropic weak bases, such as chloroquine, which sequester in these compartments, neutralize their acidity, and disrupt pH-dependent maturation and signaling [5]. However, therapeutic use is often limited by systemic safety concerns, including retinal toxicity and cardiac conduction disturbances, necessitating careful monitoring [6]. Sources: [1] Maxfield, F. R., & McGraw, T. E. (2004). Nature Reviews Molecular Cell Biology; [2] Mindell, J. A. (2012). Annual Review of Physiology; [3] Kirkegaard, T., & Jäättelä, M. (2009). Nature Reviews Cancer; [4] Wang, X., et al. (2020). Cell Research; [5] de Duve, C., et al. (1974). Biochemical Pharmacology; [6] Marmor, M. F., et al. (2016). Ophthalmology.

Other names

Acidic organellesEndolysosomal systemLysosomal compartmentEndosomal compartment

Lysosomotropism leading to pH neutralization, inhibition of acid-dependent hydrolases, and disruption of viral membrane fusion.