A5050028352- Mitochondrial Function and Pathology
- Genetic Neurodegenerative Diseases
- Fibromyalgia and Chronic Fatigue Syndrome Research
- Alzheimer's disease research and treatments
- Genetics and Neurodevelopmental Disorders
- Epigenetics and DNA Methylation
- Parkinson's Disease Mechanisms and Treatments
- Amyotrophic Lateral Sclerosis Research
- Long-Term Effects of COVID-19
- Endoplasmic Reticulum Stress and Disease
- Multiple Sclerosis Research Studies
- Autism Spectrum Disorder Research
- Metabolism, Diabetes, and Cancer
- RNA regulation and disease
- Cellular transport and secretion
- Cancer, Hypoxia, and Metabolism
- Lipid metabolism and biosynthesis
- Autophagy in Disease and Therapy
- Diabetes and associated disorders
- Photoreceptor and optogenetics research
- Circadian rhythm and melatonin
- Sirtuins and Resveratrol in Medicine
- Biochemical effects in animals
- Cerebrovascular and genetic disorders
- Lysosomal Storage Disorders Research
La Trobe University
2013-2024
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is an enigmatic condition characterized by exacerbation of symptoms after exertion (post-exertional malaise or "PEM"), and whose severity associated requirement for rest are excessive disproportionate to the fatigue-inducing activity. There no definitive molecular marker known underlying pathological mechanism condition. Increasing evidence aberrant energy metabolism suggests a role mitochondrial dysfunction in ME/CFS. Our objective...
ABSTRACT In combination with studies of post-mortem Parkinson's disease (PD) brains, pharmacological and genetic models PD have suggested that two fundamental interacting cellular processes are impaired – proteostasis mitochondrial respiration. We re-examined the role dysfunction in lymphoblasts isolated from individuals idiopathic an age-matched control group. As previously reported for various cell types, production reactive oxygen species (ROS) by was significantly elevated. However, this...
Although understanding of the biomedical basis Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is growing, underlying pathological mechanisms remain uncertain. We recently reported a reduction in proportion basal oxygen consumption due to ATP synthesis by Complex V ME/CFS patient-derived lymphoblast cell lines, suggesting mitochondrial respiratory inefficiency. This was accompanied elevated capacity, mammalian target rapamycin complex 1 (mTORC1) signaling activity and expression...
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a devastating illness whose biomedical basis now beginning to be elucidated. We reported previously that, after recovery from frozen storage, lymphocytes (peripheral blood mononuclear cells, PBMCs) ME/CFS patients die faster in culture medium than those healthy controls. also found that lymphoblastoid cell lines (lymphoblasts) derived these PBMCs exhibit multiple abnormalities mitochondrial respiratory function and signalling...
Abstract Flatworms are among the best studied animal models for regeneration; however, they also represent an emerging opportunity to investigate other biological processes as well. For instance, flatworms nocturnal and sleep during day, a state that is regulated by sleep/wake history action of sleep‐promoting neurotransmitter gamma‐aminobutyric acid (or GABA). Sleep widespread across kingdom, where it serves many nonexclusive functions. Notably, saves energy reducing metabolic rate not...
<b><i>Background:</i></b> The need for accessible cellular biomarkers of neurodegeneration in carriers the fragile X mental retardation 1 (<i>FMR1</i>) premutation (PM) alleles. <b><i>Objective:</i></b> To assess mitochondrial status and respiration blood lymphoblasts from PM manifesting X-associated tremor/ataxia syndrome (FXTAS) non-FXTAS carriers, their relationship with brain white matter lesions....
Preformed amyloid seeds increase the stability and toxicity of peptide amyloids formed from viral proteins SARS-CoV-2, these protein may cause some neurological symptoms COVID-19.
The loss of function DJ-1 caused by mutations causes a form familial Parkinson's Disease (PD). However, the role in healthy and PD cells is poorly understood. Even its subcellular localization mammalian uncertain, both cytosolic mitochondrial locations having been reported. We show here that normally located cytoplasm Dictyostelium discoideum cells. With unique life cycle, straightforward genotype-phenotype relationships, experimental accesibility genetic tractability, offers an attractive...
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is an enigmatic condition characterized by exacerbation of symptoms after exertion (post-exertional malaise or &ldquo;PEM&rdquo;), and fatigue whose severity associated requirement for rest are excessive disproportionate to the fatigue-inducing activity. There no definitive molecular marker known underlying pathological mechanism condition. Increasing evidence aberrant energy metabolism suggests a role mitochondrial...
Abstract Lipid droplets (LDs) are dynamic cellular organelles that play an essential role in lipid metabolism and storage. LD dysregulation has been implicated various diseases. However, investigations into the dynamics under disease conditions have rarely reported, possibly due to absence of high performing imaging agents. Here a novel fluorogenic probe, AM‐QTPA, is reported for specific imaging. AM‐QTPA demonstrates viscosity sensitivity aggregation‐induced emission enhancement...
Autophagy is a degradative recycling process central to the maintenance of homeostasis in all eukaryotes. By ensuring degradation damaged mitochondria, it plays key role maintaining mitochondrial health and function. Of highly conserved autophagy proteins, autophagy-related protein 1 (Atg1) essential process. The involvement these proteins intracellular signalling pathways, including those involving function, are still being elucidated. Here Atg1 was investigated simple model organism...
HTRA2 is a mitochondrial protein, mutations in which are associated with autosomal dominant late-onset Parkinson’s disease (PD). The mechanisms by result PD poorly understood. proposed to play proteolytic role protein quality control and homeostasis the intermembrane space. Its loss has been reported accumulation of unfolded misfolded proteins. However, at least one case, PD-associated mutation can cause its hyperphosphorylation, possibly resulting protease hyperactivity. consequences...
The human protein arginine methyltransferase NDUFAF7 controls the assembly of ∼1-MDa mitochondrial complex I (CI; NADH ubiquinone oxidoreductase) by methylating its subunit NDUFS2. We determined crystal structures MidA, Dictyostelium ortholog NDUFAF7. MidA catalytic core domain resembles other eukaryotic methyltransferases. However, three large loops assemble into a regulatory that is likely to control ligand selection. Binding NDUFS2 weakened methylation, suggesting mechanism for...
The fragile X premutation (PM) allele contains a CGG expansion of 55-200 repeats in the FMR1 gene's promoter. Male PM carriers have an elevated risk developing neurological and psychiatric changes, including approximately 50% Fragile X–Associated Tremor/Ataxia Syndrome (FXTAS). aim this study was to assess relationships regional white matter hyperintensities (wmhs) semi-quantitative scores, clinical status, motor (UPDRS, ICARS, Tremor) scales, cognitive impairments, with FMR1-specific...
Alpha synuclein has been linked to both sporadic and familial forms of Parkinson's disease (PD) is the most abundant protein in Lewy bodies a hallmark disease. The function this molecular mechanisms underlying its toxicity are still unclear, but many studies have suggested that mechanism α-synuclein involves alterations mitochondrial function. Here we expressed human two PD-causing mutant proteins (with point mutation, A53T, C-terminal 20 amino acid truncation) eukaryotic model
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a devastating illness whose biomedical basis now beginning to be elucidated. We reported previously that, after recovery from frozen storage, lymphocytes (peripheral blood monocytic cells, PBMCs) ME/CFS patients die faster in culture medium than those healthy controls. also found that lymphoblastoid cell lines (lymphoblasts) derived these PBMCs exhibit multiple abnormalities mitochondrial respiratory function and signalling...
Parkinson’s Disease (PD) is the second most common neurodegenerative disease world-wide. Mutations in multidomain protein Leucine Rich Repeat Kinase 2 (LRRK2) are frequent cause of hereditary PD. Furthermore, recent data suggest that independent mutations, increased kinase activity LRRK2 plays an essential role PD pathogenesis. Isolated mitochondria tissue samples from patients carrying mutations display a significant impairment mitochondrial function. However, due to complexity signaling...
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is an enigmatic condition characterized by exacerbation of symptoms after exertion (post-exertional malaise or &ldquo;PEM&rdquo;), and fatigue whose severity associated requirement for rest are excessive disproportionate to the fatigue-inducing activity. There no definitive molecular marker known underlying pathological mechanism condition. Increasing evidence aberrant energy metabolism suggests a role mitochondrial...
Fragile X Associated Tremor/Ataxia Syndrome (FXTAS) is a neurodegenerative disorder affecting carriers of premutation alleles (PM) the X-linked FMR1 gene, which contain CGG repeat expansions 55-200 range in non-coding region. This late-onset characterised by presence tremor/ataxia and cognitive decline, associated with white matter lesions throughout brain, especially involving middle cerebellar peduncles. Nearly half older male ~ 20% female PM develop FXTAS. While there evidence for...
Mitochondrial Complex II is composed of four core subunits and mutations to any the result in lowered activity. Surprisingly, although can yield similar clinical outcomes, there are distinct differences patterns disease most commonly associated with different subunits. Thus, SdhA subunit often mitochondrial phenotypes, whilst other SdhB-D more tumour formation. The reason outcomes so unknown. Here, we individually antisense-inhibited three subunits, SdhA, SdhB or SdhC, simple model organism...
Parkinson's disease is the second largest neurodegenerative worldwide and caused by a combination of genetics environment. It characterized death neurons in substantia nigra brain but not solely brain, as it affects multiple tissues organs. Studying accessible such skin blood has increased our understanding disease's pathogenesis. Here, we used lymphoblast cell lines generated from patient healthy age- sex-matched control groups obtained their whole-cell transcriptomes proteomes. Our...
The X-linked