The lysosomotrope GPN mobilises Ca from acidic organelles.

Lysosomes are acidic Ca stores often mobilised in conjunction with endoplasmic reticulum (ER) Ca stores. Glycyl-L-phenylalanine 2-naphthylamide (GPN) is a widely used lysosomotropic agent that evokes cytosolic Ca signals in many cells. However, whether these signals are the result of a primary action on lysosomes is unclear in light of recent evidence showing that GPN mediates direct ER Ca release through changes in cytosolic pH.

Managing thromboembolic risk from atrial fibrillation in patients with cancer: a role for nonpharmacologic approaches.

Atrial fibrillation (AF) in the setting of malignancy poses a unique challenge given the confluent pathologies and risks of current treatments. Oral anticoagulation is recommended to reduce the risk of systemic thromboembolism in high-risk individuals with AF. The 'Watchman' device for left atrial appendage closure has shown comparable efficacy compared with anticoagulation with warfarin; however, patients with cancer were not included in trials testing Watchman safety and efficacy.

Mining of Ebola virus entry inhibitors identifies approved drugs as two-pore channel pore blockers.

Two-pore channels (TPCs) are Ca-permeable ion channels localised to the endo-lysosomal system where they regulate trafficking of various cargoes including viruses. As a result, TPCs are emerging as important drug targets. However, their pharmacology is ill-defined.

Two-pore channels and disease.

Two-pore channels (TPCs) are Ca-permeable endo-lysosomal ion channels subject to multi-modal regulation. They mediate their physiological effects through releasing Ca from acidic organelles in response to cues such as the second messenger, NAADP. Here, we review emerging evidence linking TPCs to disease.

Connecting Ca and lysosomes to Parkinson disease.

The neurodegenerative movement disorder Parkinson disease (PD) is prevalent in the aged population. However, the underlying mechanisms that trigger disease are unclear. Increasing work implicates both impaired Ca signalling and lysosomal dysfunction in neuronal demise.