A5022227058- Peroxisome Proliferator-Activated Receptors
- Microbial Metabolic Engineering and Bioproduction
- RNA Research and Splicing
- Metabolomics and Mass Spectrometry Studies
- Lipid metabolism and biosynthesis
- RNA and protein synthesis mechanisms
- Fungal and yeast genetics research
- RNA modifications and cancer
- Mitochondrial Function and Pathology
- Cholesterol and Lipid Metabolism
- Nuclear Structure and Function
- Inflammation biomarkers and pathways
- Cancer-related gene regulation
- Inflammatory Bowel Disease
- Photosynthetic Processes and Mechanisms
- Plant biochemistry and biosynthesis
- Parkinson's Disease Mechanisms and Treatments
- Endoplasmic Reticulum Stress and Disease
- Ferroptosis and cancer prognosis
- Nuclear Receptors and Signaling
- Metabolism, Diabetes, and Cancer
- Alzheimer's disease research and treatments
- Cancer-related Molecular Pathways
- Cellular transport and secretion
- Wnt/β-catenin signaling in development and cancer
University of Alberta
2007-2023
Significance Multiple studies have implicated dozens of risk loci that may be associated with Alzheimer’s disease (AD), but common mechanisms underlying how they contribute to onset or progression remain elusive. This study identifies cell-specific roles for Drosophila orthologs AD genes in lipid droplet formation that, when disrupted, lead neurodegeneration. Our work reinforces a critical role the sequestration peroxidated lipids glia, and places Apolipoprotein E ε4 (APOE4) other factors...
During oxidative stress neurons release lipids that are internalized by glia. Defects in this coordinated process play an important role several neurodegenerative diseases. Yet, the mechanisms of lipid and its consequences on neuronal health unclear. Here, we demonstrate lipid-protein particle autolysosome exocytosis protects from ferroptosis, a form cell death driven peroxidation. We show during stress, peroxidated iron released autolysosomal which requires exocytic machinery VAMP7 syntaxin...
ApoE mediates the transport of lipids from neurons to glial lipid droplets. ApoE4, a major risk factor for Alzheimer's disease, impairs this pathway, increasing neurodegeneration. ApoE2 and ApoE3 Christchurch (ApoE3Ch) variants confer resistance developing yet little is known regarding how these protective affect transport. Here, we explored lipoprotein particles containing different isoforms neuronal health in vitro intact rodent hippocampi. We demonstrate that ApoE3Ch protect ferroptosis...
Intercellular transmission of α-synuclein contributes to Parkinson's disease pathology. Yet, the mechanisms spread are not fully understood. Here, we used live-cell microscopy examine impact associated lipid alterations on release. We discovered that increased glucosylceramides induce ectosome shedding from primary neurons, and dopaminergic neurons derived patient iPSCs harboring mutations in GBA1 (N370S, L444P W378G) LRRK2 (G2019S R1441H) compared their isogenic control. show elevated...
In Saccharomyces cerevisiae, peroxisomal inheritance from mother cell to bud is conducted by the class V myosin motor, Myo2p. However, homologues of S. cerevisiae Myo2p receptor, Inp2p, are not readily identifiable outside Saccharomycetaceae family. Here, we demonstrate an unexpected role for Pex3 proteins in peroxisome inheritance. Both Pex3p and Pex3Bp integral membrane that function as receptors through direct interaction with globular tail. cells lacking Pex3Bp, peroxisomes...
ABSTRACT The peroxin Pex11 has a recognized role in peroxisome division. Pex11p remodels and elongates peroxisomal membranes prior to the recruitment of dynamin-related GTPases that act membrane scission divide peroxisomes. We performed comprehensive comparative genomics survey understand significance evolution protein family yeast other eukaryotes. is highly conserved ancestral, undergone numerous lineage-specific duplications, whereas members are fungal-specific innovations. Functional...
ABSTRACT Eukaryotic cells have evolved molecular mechanisms to ensure the faithful inheritance of organelles by daughter in order maintain benefits afforded compartmentalization biochemical functions. Little is known about peroxisomes, lipid metabolism. We analyzed peroxisome dynamics and dimorphic yeast Yarrowia lipolytica . Most peroxisomes are anchored at periphery Y. In vivo video microscopy showed that cell division, approximately half mother dislodged individually from their static...
Dynein is a large macromolecular motor complex that moves cargo along microtubules. A motor-independent role for the light chain of dynein, Dyn2p, in peroxisome biology Saccharomyces cerevisiae was suggested from its interaction with Pex14p, component peroxisomal matrix protein import docking complex. Here we show cells yeast Yarrowia lipolytica deleted gene encoding homologue Dyn2p are impaired function and biogenesis. These exhibit compromised growth on medium containing oleic acid as...
Abstract Most soluble proteins targeted to the peroxisomal matrix contain a C‐terminal peroxisome targeting signal type 1 (PTS1) or an N‐terminal PTS2 that is recognized by receptors Pex5p and Pex7p, respectively. These cycle between cytosol back again for multiple rounds of cargo delivery peroxisome. A small number proteins, including all six isozymes fatty acyl‐CoA oxidase (Aox) yeast Yarrowia lipolytica , neither PTS1 nor PTS2. Pex20p has been shown function as co‐receptor Pex7p in import...
Summary A growing list of Alzheimer’s disease (AD) genetic risk factors is being identified, but the contribution these mutations to remains largely unknown. Accumulating data support a role lipid dysregulation and excessive ROS in etiology AD. Here, we identified cell-specific roles for eight AD risk-associated genes ROS-induced glial droplet (LD) formation. We demonstrate that LD formation requires two ABCA transporters ( ABCA1 ABCA7 ) neurons, APOE receptor LRP1 ), endocytic PICALM ,...
Background: The conformational p53-R175H is the most frequently occurring p53 mutant in cancers and a focus of targeted therapies. Plakoglobin dual cell adhesion signaling protein with tumor suppressor activity. We previously showed that plakoglobin interacts restores suppressive activity mutants, including p53-R175H, vitro. Method: Here, we used silico modeling to predict residues contribute its interaction plakoglobin, which identified Q167 R248 as involved this interaction. To validate...
A growing list of Alzheimer’s disease (AD) genetic risk factors is being identified, but the contribution these mutations to remains largely unknown. Accumulating data support a role lipid dysregulation and excessive ROS in etiology AD. Here, we identified cell-specific roles for eight AD risk-associated genes ROS-induced glial droplet (LD) formation. We demonstrate that LD formation requires two ABCA transporters (ABCA1 ABCA7) neurons, APOE receptor (LRP1), endocytic (PICALM, CD2AP, AP2A2)...
While disease-specific differences between IBD phenotypes are important, it is also of interest to see the conserved elements that reflect response injury shared by phenotypes. To map Ulcerative Colitis (UC) and ileal Crohn’s Disease (CD) we used microarrays study molecular landscape 63 UC biopsies compared 16 control colon biopsies, 37 CD 7 biopsies. These comparisons were expressed as “molecular landscapes” using volcano plots association strength via p-value (x-axis) versus fold change...
ABSTRACT During oxidative stress neurons release lipids that are internalized by glia. Defects in this coordinated process play an important role several neurodegenerative diseases. Yet, the mechanisms of lipid and its consequences on neuronal health unclear. Here, we demonstrate lipid-protein particle autolysosome exocytosis protects from ferroptosis, a form cell death driven peroxidation. We show during stress, peroxidated iron released autolysosomal which requires exocytic machinery;...