A5100347199- Coenzyme Q10 studies and effects
- Mitochondrial Function and Pathology
- Growth Hormone and Insulin-like Growth Factors
- Reproductive Biology and Fertility
- Advanced battery technologies research
- TGF-β signaling in diseases
- Biochemical Acid Research Studies
- ATP Synthase and ATPases Research
- Genetics, Aging, and Longevity in Model Organisms
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Hypothalamic control of reproductive hormones
- Birth, Development, and Health
- Kruppel-like factors research
- Genetic Syndromes and Imprinting
- Medicinal Plant Pharmacodynamics Research
- Thyroid Disorders and Treatments
- Vitamin C and Antioxidants Research
- Renal and related cancers
- RNA modifications and cancer
- Metalloenzymes and iron-sulfur proteins
- Plant and fungal interactions
- Redox biology and oxidative stress
- Heat shock proteins research
- Glutathione Transferases and Polymorphisms
- Cholesterol and Lipid Metabolism
McGill University
2015-2024
Beijing Botanical Garden
2021-2024
University of Chinese Academy of Sciences
2021-2024
South China Botanical Garden
2021-2024
Children's Hospital of Eastern Ontario
2023
University of Ottawa
2023
Ottawa Hospital
2023
University of Alabama at Birmingham
2012
Ubiquinone (UQ) is implicated in mitochondrial electron transport, superoxide generation and as a membrane antioxidant. Here we present mouse model which UQ biosynthesis can be interrupted partially restored at will. Global loss of leads to gradual function, development disease phenotypes shortened lifespan. However, find that does not act antioxidant vivo its requirement for transport much lower than anticipated, even vital mitochondria-rich organs. In fact, severely depressed function due...
Abstract Primary ubiquinone (co‐enzyme Q) deficiency results in a wide range of clinical features due to mitochondrial dysfunction. Here, we analyse and characterize two mutations the biosynthetic gene COQ7 . One mutation from only previously identified patient (V141E), one (L111P) 6‐year‐old girl who presents with spasticity bilateral sensorineural hearing loss. We used fibroblast cell lines heterologous expression system show that both lead loss protein stability decreased levels correlate...
GnRH1 stimulates the synthesis and secretion of FSH LH from anterior pituitary gland. The molecular mechanisms through which produces these effects in humans have not been determined. Here, we examined transcriptional regulation human FSHβ (FSHB) subunit using reporter assays immortalized murine gonadotrope cells. dose time dependently stimulated FSHB promoter activity, with peak stimulation occurring at 8 h. rapidly various MAPK cascades, though ERK1/2 p38 pathways appeared to be most...
Pituitary FSH regulates ovarian and testicular function. Activins stimulate FSHβ subunit (Fshb) gene transcription in gonadotrope cells, the rate-limiting step mature synthesis. Activin A-induced murine Fshb immortalized gonadotropes is dependent on homolog of Drosophila mothers against decapentaplegic (SMAD) proteins as well forkhead factor FOXL2 (FOXL2). Here, we demonstrate that synergizes with SMAD2, SMAD3, SMAD4 to promoter-reporter activity heterologous cells. Moreover, SMAD3-induction...
Mycobacterium smegmatis is a commonly used mycobacterial model system. Here, we show that M. protects itself against elevated salinity by synthesizing ectoine and hydroxyectoine characterize the phenotype of nonproducing mutant. This first analysis halotolerance molecular mechanism supports it.
Coenzyme Q10 (CoQ10) is necessary as electron transporter in mitochondrial respiration and other cellular functions. CoQ10 synthesized by all cells defects the synthesis pathway result primary deficiency that frequently leads to severe disease syndrome. exceedingly hydrophobic, insoluble, poorly bioavailable, with dietary supplementation produces no or only minimal relief for patients. We studied a patient from Turkey identified characterized new mutation biosynthetic gene COQ7 (c.161G > A;...
Abstract COQ7 encodes a hydroxylase responsible for the penultimate step of coenzyme Q10 (CoQ10) biosynthesis in mitochondria. CoQ10 is essential multiple cellular functions, including mitochondrial oxidative phosphorylation, lipid metabolism, and reactive oxygen species homeostasis. Mutations have been previously associated with primary deficiency, clinically heterogeneous multisystemic disorder. We identified biallelic variants nine families diagnosed distal hereditary motor neuropathy...
Mitochondrial electron transport chain complexes organize into supramolecular structures called respiratory supercomplexes (SCs). The role of SCs remains largely unconfirmed despite evidence supporting their necessity for mitochondrial function. mechanisms underlying the formation I
Mclk1 (also known as Coq7) and Coq3 code for mitochondrial enzymes implicated in the biosynthetic pathway of ubiquinone (coenzyme Q or UQ). Mclk1+/− mice are long-lived but have dysfunctional mitochondria. This phenotype remains unexplained, no changes UQ content were observed these mutants. By producing highly purified submitochondrial fractions, we report here that present a unique profile was characterized by decreased levels inner membrane coupled with increased outer membrane....
The development of neurodegenerative diseases such as Alzheimer, Parkinson, and Huntington disease is strongly age-dependent. Discovering drugs that act on the high rate aging in older individuals could be a means combating these diseases. Reduction activity mitochondrial enzyme CLK-1 (also known COQ7) slows down Caenorhabditis elegans mice. Clioquinol metal chelator has beneficial effects several cellular animal models well Alzheimer patients. Here we show clioquinol inhibits mammalian...
Ubiquinone (UQ), a.k.a. coenzyme Q, is a redox-active lipid that participates in several cellular processes, particular mitochondrial electron transport. Primary UQ deficiency rare but severely debilitating condition. Mclk1 (a.k.a. Coq7) encodes conserved enzyme necessary for biosynthesis. We engineered conditional knockout models to study pathogenic effects of and assess potential therapeutic agents the treatment deficiencies. found cells are viable total absence UQ. The biosynthetic...
FSH is an essential regulator of mammalian reproduction. Its synthesis by pituitary gonadotrope cells regulated multiple endocrine and paracrine factors, including TGFβ superfamily ligands, such as the activins inhibins. Activins stimulate via transcriptional regulation its β-subunit gene (Fshb). More recently, bone morphogenetic proteins (BMPs) were shown to murine Fshb transcription alone in synergy with activins. BMP2 signals canonical type I receptor, BMPR1A (or activin receptor-like...
Abstract The glycoprotein FSH, a product of pituitary gonadotrope cells, regulates ovarian follicle development in females and spermatogenesis males. FSH is heterodimer the common α gonadotropin subunit hormone-specific FSHβ (a Fshb gene). Using conditional knockout approach (Cre-lox), we previously demonstrated that expression mice depends on transcription factors forkhead box L2 (FOXL2) SMAD4. Deletion Foxl2 or Smad4 alone led to deficiency, female subfertility, oligozoospermia...
The Caenorhabditis elegans clk-1 gene and the orthologous mouse Mclk1 encode a mitochondrial hydroxylase that is necessary for biosynthesis of ubiquinone (UQ). Mutations in these genes produce broadly pleiotropic phenotypes both species, including lengthening animal lifespan. A number features C. mutants, maternal effect, particularly extensive pleiotropy, as well unexplained differences between alleles have suggested CLK-1/MCLK1 might additional functions besides UQ biosynthesis. In...