Hermansky-Pudlak syndrome 6 protein (HPS6) has originally been identified as a subunit of the BLOC-2 protein complex that is involved in the biogenesis of lysosome-related organelles. Here, we demonstrate that HPS6 directly interacts with the dynactin p150 subunit of the dynein–dynactin motor complex and acts as cargo adaptor for the retrograde motor to mediate the transport of lysosomes from t...

A major pathway to the lysosome for soluble hydrolases involves the 6-phosphorylation of mannose residues. The initial step in this reaction is catalyzed by a phosphotransferase which recognizes lysosomal precursors. We constructed mutants of human procathepsin D whose targeting to the lysosome could be assayed directly in intact cells. Eight lysine residues were individually converted to gluta...

A novel cancer cell lysosome-targetable multifunctional NO-delivery nanoplatform (Lyso-Ru-NO@FA@C-TiO2) (1) was developed. It selectively targets folate-receptor overexpressed cancer cells and specifically locates within the lysosome organelle to which NO and reactive oxygen species are simultaneously released upon 808 nm NIR light irradiation. The dual-targeted nanoplatform (1) demonstrated th...

Lysosomes are membrane-bound organelles found in every eukaryotic cell. They are widely known as terminal catabolic stations that rid cells of waste products and scavenge metabolic building blocks that sustain essential biosynthetic reactions during starvation. In recent years, this classical view has been dramatically expanded by the discovery of new roles of the lysosome in nutrient sensing, ...

Macroautophagy (hereafter referred to as autophagy) is a highly conserved cellular process that delivers proteins and organelles to the lysosome and controls the degradation of these substrates to facilitate homeostasis. In addition, it is an important process to adapt the availability of nutrients. Amino acids activate mammalian target of rapamaycin complex 1 (mTORC1), which is the key regulat...

The endosome/lysosome system in the nervous system is critically important for a variety of neuronal functions such as neurite outgrowth, retrograde transport, and synaptic plasticity. In neurons, the endosome/lysosome system is crucial for the activity-dependent internalization of membrane proteins and contributes to the regulation of lipid level on the plasma membrane. Although homeostasis of...

7-Ketocholesterol (7KC) is a cytotoxic oxysterol that plays a role in many age-related degenerative diseases. 7KC formation and accumulation often occurs in the lysosome, which hinders enzymatic transformations that reduce its toxicity and increase the sensitivity to lysosomal membrane permeabilization. We assayed the potential to mitigate 7KC cytotoxicity and enhance cell viability by overexpr...

The lysosomal/endosomal system of African trypanosomes is developmentally regulated and is important in the pathogenesis associated with infection of the mammalian bloodstream. Long considered to be a target for drug development, the internal pH of the lysosome has been variously reported to range from <5.0 to >6.0. We have refined a flow cytometric technique using a pH-sensitive probe that spe...

In response to stress conditions (such as nutrient limitation or accumulation of damaged organelles) and certain pathological situations, eukaryotic cells use autophagy as a survival mechanism. During nutrient stress the main purpose of autophagy is to degrade cytoplasmic materials within the lysosome/vacuole lumen and generate an internal nutrient pool that is recycled back to the cytosol. Thi...