A5073148691- Mitochondrial Function and Pathology
- Metabolism and Genetic Disorders
- ATP Synthase and ATPases Research
- Glaucoma and retinal disorders
- Retinal Development and Disorders
- Alzheimer's disease research and treatments
- Adipose Tissue and Metabolism
- Retinopathy of Prematurity Studies
- Genetic Neurodegenerative Diseases
- Neurological Disorders and Treatments
- CRISPR and Genetic Engineering
- Retinal Diseases and Treatments
- Traumatic Brain Injury and Neurovascular Disturbances
- Photosynthetic Processes and Mechanisms
- Pluripotent Stem Cells Research
- Neuroscience and Neuropharmacology Research
- Cholinesterase and Neurodegenerative Diseases
- RNA modifications and cancer
- Metabolomics and Mass Spectrometry Studies
- Animal Genetics and Reproduction
- Retinal and Optic Conditions
- Trace Elements in Health
- Muscle metabolism and nutrition
- Glycogen Storage Diseases and Myoclonus
- Muscle Physiology and Disorders
Centre for Eye Research Australia
2015-2025
The University of Melbourne
2015-2025
St Vincent's Hospital
2000-2024
The Royal Victorian Eye & Ear Hospital
2011-2014
Lurie Children's Hospital
2014
Northwestern University
2014
Monash Institute of Medical Research
2012
Monash University
1987-2012
St. Vincent's Birmingham
1987-2009
St Vincent's Health
2008-2009
Significance Mitochondria generate signals that regulate nuclear gene expression via retrograde signaling, but this phenomenon is rendered more complex by the quantitative differences in percentage of mutant and normal mtDNAs can exist within patient cells. This study demonstrates depending upon its relative cytoplasmic levels, a single mtDNA point mutation cause discrete set cellular transcriptional responses cells same background. qualitative regulation changes levels challenges...
Retinal ganglion cells endure significant metabolic stress in glaucoma but maintain capacity to recover function. Nicotinamide, a precursor of NAD+ , is low serum patients and its supplementation provides robust protection retinal preclinical models. However, the potential nicotinamide human unknown.To examine effects on inner function glaucoma, participants receiving concurrent therapy.Crossover, double-masked, randomized clinical trial. Participants recruited from two tertiary care...
In studies of Alzheimer's disease pathogenesis there is an increasing focus on mechanisms intracellular amyloid-β (Aβ) generation and toxicity. Here we investigated the inhibitory potential 42 amino acid Aβ peptide (Aβ 1-42 ) activity electron transport chain enzyme complexes in human mitochondria. We found that synthetic specifically inhibited terminal complex cytochrome c oxidase (COX) a dose-dependent manner was dependent presence Cu 2+ specific “aging” solution. Maximal COX inhibition...
Leber's hereditary optic neuropathy (LHON) is a form of blindness caused by mitochondrial DNA (mtDNA) mutations in complex I genes. We report an extensive biochemical analysis the defects lymphoblasts and transmitochondrial cybrids harboring three most common LHON mutations: 3460A, 11778A, 14484C. Respiration studies revealed that 3460A mutation reduced maximal respiration rate 20–28%, 11778A 30–36%, 14484C 10–15%. The transferred cybrid experiments linking these to mtDNA. Complex enzymatic...
A point mutation in the mtDNA-encoded ATP6 gene (T-->G at nt 8993) associated with Leigh syndrome two pedigrees was found to decrease ADP-stimulated (state III) respiration and ratio of ADP molecules phosphorylated oxygen atoms reduced (ADP/O ratio) but did not affect 2,4-dinitrophenol (DNP)-uncoupled respiration, suggesting a defective mitochondrial H(+)-translocating ATP synthase. Intact mitochondria isolated from patient control lymphoblastoid cell lines were tested for state III,...
purpose. The transformed RGC-5 retinal ganglion cell line is used widely in glaucoma research. Increased resistance to glutamate was noted published literature and led the recharacterization of line. methods. Characterization performed by sequencing a region nuclear Thy1 gene mitochondrial DNA d-loop tRNAPhe gene. Marker expression examined undifferentiated cells, cells differentiated with 50 μg/mL succinyl concanavalin A (S Con A) for 3 days. Glutamate sensitivity S...
DNA methylation is an essential mechanism controlling gene expression during differentiation and development. We investigated the epigenetic regulation of nuclear-encoded, mitochondrial (mtDNA) polymerase γ catalytic subunit ( PolgA ) by examining status a CpG island within exon 2 PolgA. Bisulphite sequencing identified low levels (<10%) mouse oocytes, blastocysts embryonic stem cells (ESCs), while somatic tissues contained significantly higher (>40%). In contrast, induced pluripotent (iPS)...
Author(s): Tezel, Gulgun; Fourth ARVO/Pfizer Ophthalmics Research Institute Conference Working Group
Oxidative phosphorylation (OXPHOS) drives ATP production by mitochondria, which are dynamic organelles, constantly fusing and dividing to maintain kidney homoeostasis. In diabetic disease (DKD), mitochondria appear dysfunctional, but the temporal development of diabetes-induced adaptations in mitochondrial structure bioenergetics have not been previously documented. present study, we map changes dynamics function rat at 4, 8, 16 32 weeks diabetes. Our data reveal that precede albuminuria...
Purpose.: Following the recent demonstration of increased mitochondrial DNA mutations in lymphocytes POAG patients, authors sought to characterize function a separate cohort POAG. Methods.: Using similar methodology that previous applied Leber's hereditary optic neuropathy (LHON) maximal adenosine triphosphate (ATP) synthesis and cellular respiration rates, as well cell growth rates glucose galactose media, were assessed transformed from patients (n = 15) group age- sex-matched controls 15)....
Obesity is associated with chronic low-grade inflammation that contributes to defects in energy metabolism and insulin resistance. Suppressor of cytokine signaling (SOCS)-3 expression increased skeletal muscle obese humans. SOCS3 inhibits leptin the hypothalamus signal transduction adipose tissue liver. Skeletal an important for controlling expenditure whole-body sensitivity; however, physiological importance this has not been examined. Therefore, we generated mice had specifically deleted...
Primary Open Angle Glaucoma (POAG) is a common neurodegenerative disease characterized by the selective and gradual loss of retinal ganglion cells (RGCs). Aging increased intraocular pressure (IOP) are glaucoma risk factors; nevertheless patients deteriorate at all levels IOP, implying other causative factors. Recent evidence presents mitochondrial oxidative phosphorylation (OXPHOS) complex-I impairments in POAG. Leber Hereditary Optic Neuropathy (LHON) suffer specific rapid RGCs,...
A heteroplasmic G-to-A transition at nucleotide pair (np) 14459 within the mitochondrial DNA (mtDNA)encoded NADH dehydrogenase subunit 6 (ND6) gene has been identified as cause of Leber hereditary optic neuropathy (LHON) and/or pediatric-onset dystonia in three unrelated families.This ND6 np mutation changes a moderately conserved alanine to valine amino acid position 72 protein.Enzymologic analysis (complex I) with submitochondrial particles isolated from Epstein-Barr virus-transformed...
Eukaryotic cells devoid of mitochondrial DNA (rho0 cells) were originally generated under artificial growth conditions utilizing ethidium bromide. The chemical is known to intercalate preferentially with the double-stranded thereby interfering enzymes replication machinery. Rho0 cell lines are highly valuable tools study human disorders because they can be utilized in cytoplasmic transfer experiments. However, mutagenic effects bromide onto nuclear cannot excluded. To foreclose this...
Radiolabeled diacetylbis(4-methylthiosemicarbazonato)copper II [Cu (atsm)] is an effective positron-emission tomography imaging agent for myocardial ischemia, hypoxic tumors, and brain disorders with regionalized oxidative stress, such as mitochondrial myopathy, encephalopathy, lactic acidosis stroke-like episodes (MELAS) Parkinson’s disease. An excessively elevated reductive state common to these conditions has been proposed important mechanism affecting cellular retention of Cu from...