Acidic organelles

Acidic organelles, primarily comprising lysosomes and late endosomes, are specialized membrane-bound compartments maintained at a low internal pH (typically 4.5–5.5) by the action of vacuolar-type H+-ATPases (V-ATPases) (Mindell, 2012, Annu Rev Physiol). This acidic environment is critical for the optimal function of acid hydrolases that degrade macromolecules, as well as for processes like autophagy, nutrient recycling, and the maturation of endocytic vesicles (De Duve et al., 1974, Biochem Pharmacol). In pathological states such as cancer, cells often exhibit altered lysosomal biogenesis and increased acidification to support metabolic demands and facilitate invasion; conversely, in malaria, the parasite's acidic food vacuole is essential for hemoglobin digestion (Kirkegaard & Jäättelä, 2009, Semin Cancer Biol). Pharmacologically, these organelles are targeted by lysosomotropic agents—weakly basic drugs like chloroquine—which accumulate within the lumen via pH trapping, thereby neutralizing the acidity and inhibiting downstream biological pathways (Homewood et al., 1972, Nature). Therapeutic strategies also include the use of V-ATPase inhibitors or agents that trigger lysosomal membrane permeabilization to induce programmed cell death in resistant tumors (Kaufmann et al., 2009, Autophagy).

Other names

LysosomesEndosomesAcidic vacuolesLate endosomesLytic vacuoles

Drugs typically interact with acidic organelles through lysosomotropism, where weak bases cross the membrane and become protonated and trapped in the acidic lumen, leading to pH neutralization. Other mechanisms include the direct inhibition of the vacuolar-type H+-ATPase (V-ATPase) to prevent acidification or the induction of lysosomal membrane permeabilization (LMP) to release cytotoxic hydrolases into the cytosol.