Lysosomal labile iron pool (Lysosomal LIP) (Lysosomal LIP)

The lysosomal labile iron pool (LIP) represents a transient population of redox-active ferrous iron (Fe2+) maintained within the acidic lumen of lysosomes. This pool is primarily generated through the autophagic degradation of iron-containing proteins and organelles, such as ferritin (ferritinophagy) and mitochondria (mitophagy) (Mancias et al., 2014, Nature). Biologically, it serves as a critical hub for cellular iron recycling, but its high reactivity makes it a potent source of hydroxyl radicals via Fenton chemistry if not strictly regulated (Dixon et al., 2012, Cell). In many cancer types, the lysosomal LIP is significantly expanded to support rapid proliferation, a phenomenon termed "iron addiction," which creates a therapeutic vulnerability (Mai et al., 2017, Nature Chemistry). Drugs like artesunate and salinomycin exploit this pool by reacting with Fe2+ to generate lethal reactive oxygen species, triggering ferroptosis or lysosomal membrane permeabilization (Weber et al., 2020, Free Radical Biology and Medicine). Conversely, lysosome-targeted iron chelators are being investigated to protect neurons from iron-mediated oxidative stress in neurodegenerative diseases (Tenopoulou et al., 2007, Free Radical Biology and Medicine).

Other names

Labile Fe2+ pool in lysosomesLysosomal labile Fe2+ poolIntralysosomal labile ironLysosomal ferrous iron poolLysosomal LIP

Iron-mediated prodrug activation, iron sequestration, induction of ferroptosis, and lysosomal membrane permeabilization.