Calcium homeostasis in aging neurons

The nervous system becomes increasingly vulnerable to insults and prone to dysfunction during ageing. Age-related decline of neuronal function is manifested by the late onset of many neurodegenerative disorders, as well as by reduced signalling and processing capacity of individual neuron populations. Recent findings indicate that impairment of Ca2+ homeostasis underlies the increased susceptibility of neurons to damage, associated with the ageing process. However, the impact of ageing on Ca2+ homeostasis in neurons remains largely unknown. Here, we survey the molecular mechanisms that mediate neuronal Ca2+ homeostasis and discuss the impact of ageing on their efficacy. To address the question of how ageing impinges on Ca2+ homeostasis, we consider potential nodes through which mechanisms regulating Ca2+ levels interface with molecular pathways known to influence the process of ageing and senescent decline. Delineation of this crosstalk would facilitate the development of interventions aiming to fortify neurons against age-associated functional deterioration and death by augmenting Ca2+ homeostasis

Prohibitin and mitochondrial biology

8 pages, 2 figures.--PMID: 19733482 [PubMed]Prohibitins are ubiquitous, evolutionarily conserved proteins that are mainly localized in mitochondria. The mitochondrial prohibitin complex comprises two subunits, PHB1 and PHB2. These two proteins assemble into a ring-like macromolecular structure at the inner mitochondrial membrane and are implicated in diverse cellular processes: from mitochondrial biogenesis and function to cell death and replicative senescence. In humans, prohibitins have been associated with various types of cancer. While their biochemical function remains poorly understood, studies in organisms ranging from yeast to mammals have provided significant insights into the role of the prohibitin complex in mitochondrial biogenesis and metabolism. Here we review recent studies and discuss their implications for deciphering the function of prohibitins in mitochondriaThis work was supported by the European Commission Coordination Action ENINET (contract number LSHM-CT-2005-19063).Peer reviewe

Death by necrosis

Cells suffer necrotic death when exposed to extreme environmental conditions, adverse and excessive stimuli, or when deleterious mutations are encoded in their genetic material. Unlike apoptosis, which involves a highly regulated and elaborate network of biochemical events and cascades, necrosis has been considered generally to be a chaotic decadence process that effects the inexorable demise of cells otherwise not destined to die. This grim prospect is now slowly being overturned, mostly by exciting new findings in two simple model organisms, Caenorhabditis elegans and Drosophila melanogaster. Despite the wide spectrum of necrosis-initiating conditions, evidence is accumulating that execution of necrotic or neurodegenerative cell death may be carried out by a finite common set of mechanisms. Introduction Early pioneering studies of cell death delineated two major, morphologically distinct types: apoptosis and necrosis Necrosis, the second type of cell death, is radically different from apoptosis in almost every respect. The term derives from the Greek kernel 'necros', meaning 'dead' (with a sense of dismay), and refers to the accidental death of cells exposed to extreme environmental or genetically encoded insults Injured cells undergoing necrosis display gross morphological and ultra structural features that contrast sharply with those exhibited by cells undergoing apoptosis. Death is accompanied by extensive swelling of the cell, distension of various cellular organelles, clumping and random degradation of nuclear DNA, extensive plasma membrane endocytosis and autophagy It is striking that despite the profound impact of necrotic cell death on human health, the molecular events that transpire during cellular necrosis remain obscure. The dominant concept that has permeated the field stipulated that necrotic death is merely the chaotic breakdown of a cell under intolerable conditions, involving execution mechanisms almost as diverse as the triggers initiating cell death. However, relatively recent observations in simple model organisms such as Caenorhabditis elegans and Drosophila challenge these view

Lysosomal biogenesis and function is critical for necrotic cell death in Caenorhabditis elegans

Necrotic cell death is defined by distinctive morphological characteristics that are displayed by dying cells (Walker, N.I., B.V. Harmon, G.C. Gobe, and J.F. Kerr. 1988. Methods Achiev. Exp. Pathol. 13:18–54). The cellular events that transpire during necrosis to generate these necrotic traits are poorly understood. Recent studies in the nematode Caenorhabditis elegans show that cytoplasmic acidification develops during necrosis and is required for cell death (Syntichaki, P., C. Samara, and N. Tavernarakis. 2005. Curr. Biol. 15:1249–1254). However, the origin of cytoplasmic acidification remains elusive. We show that the alkalization of endosomal and lysosomal compartments ameliorates necrotic cell death triggered by diverse stimuli. In addition, mutations in genes that result in altered lysosomal biogenesis and function markedly affect neuronal necrosis. We used a genetically encoded fluorescent marker to follow lysosome fate during neurodegeneration in vivo. Strikingly, we found that lysosomes fuse and localize exclusively around a swollen nucleus. In the advanced stages of cell death, the nucleus condenses and migrates toward the periphery of the cell, whereas green fluorescent protein–labeled lysosomal membranes fade, indicating lysosomal rupture. Our findings demonstrate a prominent role for lysosomes in cellular destruction during necrotic cell death, which is likely conserved in metazoans

The Genomes On Line Database (GOLD) v.2: a monitor of genome projects worldwide

The Genomes On Line Database (GOLD) is a web resource for comprehensive access to information regarding complete and ongoing genome sequencing projects worldwide. The database currently incorporates information on over 1500 sequencing projects, of which 294 have been completed and the data deposited in the public databases. GOLD v.2 has been expanded to provide information related to organism properties such as phenotype, ecotype and disease. Furthermore, project relevance and availability information is now included. GOLD is available at . It is also mirrored at the Institute of Molecular Biology and Biotechnology, Crete, Greece a

Genome-wide investigation reveals pathogen-specific and shared signatures in the response of Caenorhabditis elegans to infection

Microarray analysis of the transcriptional response of C. elegans to four bacterial pathogens revealed that different infections trigger responses, some of which are common to all four pathogens, such as necrotic cell death, which has been associated with infection in humans

The Genomes On Line Database (GOLD) in 2007: status of genomic and metagenomic projects and their associated metadata

The Genomes On Line Database (GOLD) is a comprehensive resource that provides information on genome and metagenome projects worldwide. Complete and ongoing projects and their associated metadata can be accessed in GOLD through pre-computed lists and a search page. As of September 2007, GOLD contains information on more than 2900 sequencing projects, out of which 639 have been completed and their sequence data deposited in the public databases. GOLD continues to expand with the goal of providing metadata information related to the projects and the organisms/environments towards the Minimum Information about a Genome Sequence’ (MIGS) guideline. GOLD is available at http://www.genomesonline.org and has a mirror site at the Institute of Molecular Biology and Biotechnology, Crete, Greece at http://gold.imbb.forth.gr