... the small molecule Y102. Treatment of cells with Y102 perturbed autophagy, mitophagy and lysosome positioning in NF1 -deficient cells. A dual proteomics approach identified BLOC-one-related complex (BORC), which is required for lysosome positioning and trafficking, as a potential target of Y102. Knockdown...

... applicability was accessed throughout the Plasmodium liver stage, showing isotropic five-fold expansion. Furthermore, we used PS-ExM to visualise parasite mitochondria as well as the association of lysosomes to the parasitophorous vacuole membrane (PVM) as an example of visualising host–pathogen interaction. We...

...Eugenia Almacellas; Caroline Mauvezin ABSTRACT Lysosomes exert pleiotropic functions to maintain cellular homeostasis and degrade autophagy cargo. Despite the great advances that have boosted our understanding of autophagy and lysosomes in both physiology and pathology, their function in mitosis...

...Yuan Gao; Juan Xiong; Qing-Zhu Chu; Wei-Ke Ji ABSTRACT Membrane contact sites (MCSs) between the endoplasmic reticulum (ER) and late endosomes/lysosomes (LE/lys) are emerging as critical hubs for diverse cellular events, and changes in their extents are linked to severe neurological diseases. While...

...Yu Yuan; Bethan S. Kilpatrick; Susanne Gerndt; Franz Bracher; Christian Grimm; Anthony H. Schapira; Sandip Patel ABSTRACT Lysosomes are acidic Ca 2+ stores often mobilised in conjunction with endoplasmic reticulum (ER) Ca 2+ stores. Glycyl-L-phenylalanine 2-naphthylamide (GPN) is a widely used...

.... lysosomes, mitochondria and peroxisomes) by taking advantage of the extraordinarily high affinity between the twin strep tag and streptavidin variants. With this method, we can isolate desired organelles with high purity and yield in 3 min from the post-nuclear supernatant of mammalian cells or less than 8...

... extensively studied the dynamics of this response using both live-cell imaging and correlative light-electron microscopy (CLEM), and found that it correlates with lysosomal damage and is characterised by the recruitment of the selective autophagy-associated proteins TANK-binding kinase 1 (TBK1) and optineurin...

...Christopher H. Choy; Golam Saffi; Matthew A. Gray; Callen Wallace; Roya M. Dayam; Zhen-Yi A. Ou; Guy Lenk; Rosa Puertollano; Simon C. Watkins; Roberto J. Botelho ABSTRACT Lysosomes receive and degrade cargo from endocytosis, phagocytosis and autophagy. They also play an important role in sensing...

...Bethan S. Kilpatrick; Elizabeth Yates; Christian Grimm; Anthony H. Schapira; Sandip Patel ABSTRACT Transient receptor potential (TRP) mucolipins (TRPMLs), encoded by the MCOLN genes, are patho-physiologically relevant endo-lysosomal ion channels crucial for membrane trafficking. Several lines...

...Gennaro Napolitano; Andrea Ballabio ABSTRACT The transcription factor EB (TFEB) plays a pivotal role in the regulation of basic cellular processes, such as lysosomal biogenesis and autophagy. The subcellular localization and activity of TFEB are regulated by mechanistic target of rapamycin (mTOR...

... function in these cells remains unknown. Here, we show that rapsyn plays an AChR-independent role in organizing the distribution and mobility of lysosomes. In cells devoid of AChRs, rapsyn selectively induces the clustering of lysosomes at high density in the juxtanuclear region without affecting...

... organelles. The relevance of these ubiquitous proteins for human disease, however, is unclear. Here, we report that lysosomes are enlarged and aggregated in fibroblasts from Parkinson disease patients with the common G2019S mutation in LRRK2. Defects were corrected by molecular silencing of TPC2...

...Christopher J. Penny; Bethan S. Kilpatrick; Jung Min Han; James Sneyd; Sandip Patel ABSTRACT Acidic organelles form an important intracellular Ca 2+ pool that can drive global Ca 2+ signals through coupling with endoplasmic reticulum (ER) Ca 2+ stores. Recently identified lysosome–ER membrane...

...Thomas Burgoyne; Rushee Jolly; Belen Martin-Martin; Miguel C. Seabra; Rosanna Piccirillo; Maria Vittoria Schiaffino; Clare E. Futter Summary Multivesicular endosomes/bodies (MVBs) deliver proteins, such as activated EGF receptor (EGFR), to the lysosome for degradation, and, in pigmented cells, MVBs...

...Taeko Soma-Nagae; Shigeyuki Nada; Mari Kitagawa; Yusuke Takahashi; Shunsuke Mori; Chitose Oneyama; Masato Okada Summary The lysosomal adaptor protein p18 is an essential anchor of a scaffolding complex for the mTORC1 and MAPK pathways, which play crucial roles in controlling cell growth and energy...

...: some is recycled to the plasma membrane via Rab11-labelled recycling endosomes; the remaining PrP Sc is subject to retromer-mediated retrograde transport to the Golgi. This pathway leads to lysosomal degradation, and we show that this is the dominant PrP Sc degradative mechanism in the early stages...

... remains unclear. Here we show that rapid osmotic permeabilisation of lysosomes evokes prolonged, spatiotemporally complex Ca 2+ signals in primary cultured human fibroblasts. These Ca 2+ signals comprised an initial response that correlated with lysosomal disruption and secondary long-lasting spatially...

...Silvia Vergarajauregui; Jose A. Martina; Rosa Puertollano Loss-of-function mutations in mucolipin 1 (MCOLN1) result in mucolipidosis type IV (MLIV), a lysosomal storage disorder characterized by severe mental and psychomotor retardation. MCOLN1 is a lysosomal ion channel that belongs...

...Cinzia Progida; Laura Cogli; Francesco Piro; Azzurra De Luca; Oddmund Bakke; Cecilia Bucci Rab7b is a recently identified member of the Rab GTPase protein family and has high similarity to Rab7. It has been reported that Rab7b is lysosome associated, that it is involved in monocytic differentiation...

...Roberta Kiffin; Susmita Kaushik; Mei Zeng; Urmi Bandyopadhyay; Cong Zhang; Ashish C. Massey; Marta Martinez-Vicente; Ana Maria Cuervo Rates of autophagy, the mechanism responsible for lysosomal clearance of cellular components, decrease with age. We have previously described an age-related decline...