A5085780157- Autophagy in Disease and Therapy
- Cellular transport and secretion
- Endoplasmic Reticulum Stress and Disease
- Lysosomal Storage Disorders Research
- Calcium signaling and nucleotide metabolism
- Mitochondrial Function and Pathology
- ATP Synthase and ATPases Research
- Ubiquitin and proteasome pathways
- Toxoplasma gondii Research Studies
- Parkinson's Disease Mechanisms and Treatments
- Glycosylation and Glycoproteins Research
- RNA modifications and cancer
- Sirtuins and Resveratrol in Medicine
- Calpain Protease Function and Regulation
- Adenosine and Purinergic Signaling
- Cannabis and Cannabinoid Research
- Peptidase Inhibition and Analysis
- Signaling Pathways in Disease
- Advanced Glycation End Products research
- Immunotherapy and Immune Responses
- Lipid metabolism and biosynthesis
- Erythrocyte Function and Pathophysiology
- Advanced Fluorescence Microscopy Techniques
- T-cell and B-cell Immunology
- Photosynthetic Processes and Mechanisms
University of Helsinki
2014-2025
University of Turku
2018-2025
University of Michigan
2001-2012
Washtenaw Community College
2012
UiT The Arctic University of Norway
2012
Dalhousie University
2009
Kiel University
2003-2008
Columbia University
2001-2003
Addenbrooke's Hospital
2003
Albert Einstein College of Medicine
2003
Malignant cells often display defects in autophagy, an evolutionarily conserved pathway for degrading long-lived proteins and cytoplasmic organelles. However, as yet, there is no genetic evidence a role of autophagy genes tumor suppression. The beclin 1 gene monoallelically deleted 40–75% cases human sporadic breast, ovarian, prostate cancer. Therefore, we used targeted mutant mouse model to test the hypothesis that monoallelic deletion promotes tumorigenesis. Here show heterozygous...
Both dauer formation (a stage of developmental arrest) and adult life-span in Caenorhabditis elegans are negatively regulated by insulin-like signaling, but little is known about cellular pathways that mediate these processes. Autophagy, through the sequestration delivery cargo to lysosomes, major route for degrading long-lived proteins cytoplasmic organelles eukaryotic cells. Using nematodes with a loss-of-function mutation signaling pathway, we show bec-1 , C. ortholog yeast mammalian...
The small GTP binding protein Rab7 has a role in the late endocytic pathway and lysosome biogenesis. of mammalian autophagy is, however, unknown. We have addressed this by inhibiting function with RNA interference overexpression dominant negative Rab7. show here that was needed for formation preferably perinuclear, large aggregates, where autophagosome marker LC3 colocalised endosomal lysosomal markers. By electron microscopy we showed these aggregates corresponded to autophagic vacuoles...
The eIF2α kinases are a family of evolutionarily conserved serine/threonine that regulate stress-induced translational arrest. Here, we demonstrate the yeast kinase, GCN2 , target phosphorylation site Gcn2p, Ser-51 eIF2α, and eIF2α-regulated transcriptional transactivator, GCN4 essential for another fundamental stress response, starvation-induced autophagy. mammalian IFN-inducible PKR, rescues autophagy in -disrupted yeast, pkr null nonphosphorylatable mutant murine embryonic fibroblasts...
Autophagosomes have been reported to form in the vicinity of endoplasmic reticulum (ER). In many cases, phagophore membrane is observed between two cisternae rough ER, but it not known whether these membranes are directly connected. To investigate relationship and we used electron microscopic tomography serum amino acid starved normal rat kidney cells. The cells were fixed glutaraldehyde reduced osmium tetroxide embedded Epon. Dual axis tilt image series acquired from successive 250-nm...
Autophagic cell death is morphologically characterized by an accumulation of autophagic vacuoles. Here, we show that inactivation LAMP2 RNA interference or homologous recombination leads to vacuolization in nutrient-depleted cells. Cells lack expression showed enhanced vacuoles carrying the marker LC3, yet a decreased colocalization LC3 and lysosomes, suggesting fusion between lysosomes was inhibited. While fraction mitochondria from starved LAMP2-expressing cells colocalized with lysosomal...
The study of autophagy is rapidly expanding, and our knowledge the molecular mechanism its connections to a wide range physiological processes has increased substantially in past decade. vocabulary associated with grown concomitantly. In fact, it difficult for readers--even those who work field--to keep up ever-expanding terminology various autophagy-related processes. Accordingly, we have developed comprehensive glossary terms that meant provide quick reference researchers need brief...
Abstract Autophagy contributes to the selective degradation of liquid droplets, including P-Granule, Ape1-complex and p62/SQSTM1-body, although molecular mechanisms physiological relevance remain unclear. In this report, we describe properties endogenous p62-bodies, effect autophagosome biogenesis on these bodies, in vivo significance their turnover. p62-bodies are low-liquidity gels containing ubiquitin core autophagy-related proteins. Multiple autophagosomes form p62-gels, interaction...
Cellular homoeostatic pathways such as macroautophagy (hereinafter autophagy) are regulated by basic mechanisms that conserved throughout the eukaryotic kingdom. However, it remains poorly understood how these further evolved in higher organisms. Here we describe a modification autophagy pathway vertebrates, which promotes its activity response to oxidative stress. We have identified two oxidation-sensitive cysteine residues prototypic receptor SQSTM1/p62, allow activation of pro-survival...
In LAMP-2–deficient mice autophagic vacuoles accumulate in many tissues, including liver, pancreas, muscle, and heart. Here we extend the phenotype analysis using cultured hepatocytes. hepatocytes half-life of both early late was prolonged as evaluated by quantitative electron microscopy. However, an endocytic tracer reached vacuoles, indicating delivery endo/lysosomal constituents to vacuoles. Enzyme activity measurements showed that trafficking some lysosomal enzymes lysosomes impaired....
Mice double deficient in LAMP-1 and -2 were generated. The embryos died between embryonic days 14.5 16.5. An accumulation of autophagic vacuoles was detected many tissues including endothelial cells Schwann cells. Fibroblast cell lines derived from the double-deficient accumulated autophagy protein LC3II after amino acid starvation. Lysosomal vesicles larger more peripherally distributed showed a lower specific density Percoll gradients when compared with control enzyme activities, cathepsin...