How to make a lysosome oated vesicles had been described as early as 1961. These small membranous structures were characterized by a highly organized layer of material on the cytoplasmic surface, “but no one knew their function,” says Marilyn Farquhar, whose lab at the time had become interested in how the Golgi complex helped produce enzymes. Roth and Porter (1964) had provided evidence that c...

Autophagic lysosome reformation (ALR) is a cellular process in which lysosomes are reformed through scission of protolysosomes from tubular structures extruded from autolysosomes. Despite recent progress, the molecular mechanism of ALR is far from clear. A paper in this issue of The EMBO Journal has identified lysosome-localized PI(3)P, which is generated by the VPS34–UVRAG complex in an mTOR-d...

Autophagosome-lysosome fision measured by means o f electroinjected [ ‘“C] lactose While [‘“C] sucrose is an inert sequestration probe which eventually accumulates in lysosomes, [‘“c] lactose is hydrolysed immediately upon entry into the lysosome, by the lysosomal enzyme 0-galactosidase. Autophagically sequestered [“C] lactose therefore rapidly equilibrates at a low steady-state level, probably...

TOR complex 1 (TORC1) is a potent anabolic regulator of cellular growth and metabolism. When cells have sufficient amino acids, TORC1 is active due to its lysosomal localization mediated via the Rag GTPases. Upon amino acid removal, the Rag GTPases release TORC1, causing it to become cytoplasmic and inactive. We show here that, upon amino acid removal, the Rag GTPases also recruit TSC2 to the l...

Lysosome function is essential to many physiological processes. It has been suggested that deregulation of lysosome function could contribute to cancer. Through a genetic screen in Drosophila, we have discovered that mutations disrupting lysosomal degradation pathway components contribute to tumor development and progression. Loss-of-function mutations in the Class C vacuolar protein sorting (V...

Autophagy is a conserved cellular process to degrade and recycle cytoplasmic components. During autophagy, lysosomes fuse with an autophagosome to form an autolysosome. Sequestered components are degraded by lysosomal hydrolases and presumably released into the cytosol by lysosomal efflux permeases. Following starvation-induced autophagy, lysosome homeostasis is restored by autophagic lysosome ...

Mutations of the Plekhm1 gene in humans and rats cause osteopetrosis, an inherited bone disease characterized by diminished bone resorption by osteoclasts. PLEKHM1 binds to RAB7 and is critical for lysosome trafficking. However, the molecular mechanisms by which PLEKHM1 regulates lysosomal pathways remain unknown. Here, we generated germline and conditional Plekhm1-deficient mice. These mice di...

Late endocytic organelles including lysosomes are highly dynamic acidic organelles. Late endosomes and lysosomes directly fuse for content mixing to form hybrid organelles, from which lysosomes are reformed. It is not fully understood how these processes are regulated and maintained. Here we show that the Caenorhabditis elegans ARL-8 GTPase is localized primarily to lysosomes and involved in la...

In this study, we showed that the dual addition of glucosyl ceramide synthase and ceramidase inhibitors to A549 cell culture led to the possibility of ceramide channel formation via endogenous palmitoyl-ceramide accumulation with an increase in cholesterol contents in the lysosome membrane as an initial step prior to initiation of necrotic cell death. In addition, the dual addition led to black...

1. Lysosome-rich fractions were obtained from foetal liver tissues as early as 35 days uterine age. Foetal lysosomes showed the same ;structure-linked latency' and acid hydrolytic potentiality characteristic of their adult counterparts. 2. The osmotic stability of lysosome-rich fraction from foetal guinea-pig liver tissue was greater than that of the corresponding adult lysosome fractions, p-ni...