Alzheimer's disease (AD) is characterized by slowly progressive neuronal death, but its molecular cascade remains elusive for over 100 years. Since accumulation of autophagic vacuoles (also called granulo-vacuolar degenerations) represents one of the pathologic hallmarks of degenerating neurons in AD, a causative connection between autophagy failure and neuronal death should be present. The aim...

Endothelial cells subjected to glycated collagen I develop premature senescence within 3-5 days, as revealed by increased senescence-associated beta-galactosidase activity, decreased proliferation, and an increase in cell size. Here, we analyzed the time course and possible mechanisms of this process. Lysosomal integrity studies revealed a rapid collapse of pH gradient and lysosomal permeabiliz...

Lysosomes serve as the cellular recycling centre and are filled with numerous hydrolases that can degrade most cellular macromolecules. Lysosomal membrane permeabilization and the consequent leakage of the lysosomal content into the cytosol leads to so-called "lysosomal cell death". This form of cell death is mainly carried out by the lysosomal cathepsin proteases and can have necrotic, apoptot...

Trypanosoma cruzi enters host cells via formation of an acidic vacuole which is subsequently disrupted, allowing the parasite access to the cytoplasm. We show that in an acid environment, release of the parasite surface neuraminidase is enhanced, and this release is likely mediated by a phosphatidylinositol-specific phospholipase C (PIPLC), since antibodies to a carbohydrate epitope (CRD) revea...

Lysosomes are acidic compartments filled with more than 60 different types of hydrolases. They mediate the degradation of extracellular particles from endocytosis and of intracellular components from autophagy. The digested products are transported out of the lysosome via specific catabolite exporters or via vesicular membrane trafficking. Lysosomes also contain more than 50 membrane proteins a...

A growing body of evidence suggests that lysosomes, which have traditionally been regarded as degradative organelles, can function as Ca2+ stores, regulated by the second messenger nicotinic acid adenine dinucleotide phosphate (NAADP). We previously demonstrated that in hippocampal pyramidal neurons, activity-dependent Ca2+ release from these stores triggers fusion of the lysosome with the plas...

Programmed cell death involving lysosomal membrane permeabilization (LMP) is an alternative cell death pathway induced under various cellular conditions and by numerous cytotoxic stimuli. The method presented here to quantify LMP takes advantage of the detergent digitonin, which creates pores in cellular membranes by replacing cholesterol. The difference in cholesterol content between the plasm...

• TMEM175 encodes a lysosomal K + channel gated by AKT in kinase-independent way. A variant which increases risk of Parkinson’s reduces activity. decreases activity but only upon starvation. Knockout mice induces like pathology vivo . deficiency may deregulate Ca 2+ dynamics secondary to changes membrane potential.

Cyanidin-3-glucoside (C3G) is the most common anthocyanin in dark grains and berries a food functional factor to improve visual health. However, mechanisms of C3G on blue light-induced retinal pigment epithelial (RPE) cell photooxidative damage needs further exploration. We investigated effects light-irradiated A2E-containing RPE cells explored whether sphingolipid, mitogen-activated protein ki...

BACKGROUND Mitochondrial dysfunction and degradation takes a central role in current paradigms of neurodegeneration in Parkinson's disease (PD). Loss of DJ-1 function is a rare cause of familial PD. Although a critical role of DJ-1 in oxidative stress response and mitochondrial function has been recognized, the effects on mitochondrial dynamics and downstream consequences remain to be determine...