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Estimating the occurrence of primary ubiquinone deficiency by analysis of large-scale sequencing data

Developmental Biology. Author information AffiliationsDepartment of Biology, McGill University, Montreal, CanadaBryan G. Hughes, Paul M. Harrison & Siegfried Hekimi AuthorsSearch for Bryan G. Hughes in:Nature ... Research journals • PubMed • Google Scholar Search for Paul M. Harrison in:Nature Research journals • PubMed • Google Scholar Search for Siegfried Hekimi in:Nature Research journals • PubMed • Google

A single biochemical activity underlies the pleiotropy of the aging-related protein CLK-1

The Caenorhabditis elegans clk-1 gene and the orthologous mouse gene Mclk1 encode a mitochondrial hydroxylase that is necessary for the biosynthesis of ubiquinone (UQ). Mutations in these genes produce broadly pleiotropic phenotypes in both species, including a lengthening of animal lifespan. A number of features of the C. elegans clk-1 mutants, including a maternal effect...

Mitochondrial function and lifespan of mice with controlled ubiquinone biosynthesis

, McGill University, Montreal, Quebec, Canada H3A 1B1Ying Wang, Daniella Oxer & Siegfried Hekimi AuthorsSearch for Ying Wang in:Nature Research journals • PubMed • Google ScholarSearch for Daniella Oxer ... in:Nature Research journals • PubMed • Google ScholarSearch for Siegfried Hekimi in:Nature Research journals • PubMed • Google Scholar Contributions Y.W. and D.O. carried out the experiments. S.H. and Y.W

Mitochondrial respiration without ubiquinone biosynthesis

Ubiquinone (UQ), a.k.a. coenzyme Q, is a redox-active lipid that participates in several cellular processes, in particular mitochondrial electron transport. Primary UQ deficiency is a rare but severely debilitating condition. Mclk1 (a.k.a. Coq7) encodes a conserved mitochondrial enzyme that is necessary for UQ biosynthesis. We engineered conditional Mclk1 knockout models to study...

A Mild Impairment of Mitochondrial Electron Transport Has Sex-Specific Effects on Lifespan and Aging in Mice

Impairments of various aspects of mitochondrial function have been associated with increased lifespan in various model organisms ranging from Caenorhabditis elegans to mice. For example, disruption of the function of the ‘Rieske’ iron-sulfur protein (RISP) of complex III of the mitochondrial electron transport chain can result in increased lifespan in the nematode worm C. elegans...

A Mitochondrial Superoxide Signal Triggers Increased Longevity in Caenorhabditis elegans

The study of long-lived C. elegans mutants suggests that mitochondrial oxidants can actually help reduce aging by acting as stress signals, rather than acting solely as toxic molecules.

Mitochondrial and Cytoplasmic ROS Have Opposing Effects on Lifespan

Reactive oxygen species (ROS) are highly reactive, oxygen-containing molecules that can cause molecular damage within the cell. While the accumulation of ROS-mediated damage is widely believed to be one of the main causes of aging, ROS also act in signaling pathways. Recent work has demonstrated that increasing levels of superoxide, one form of ROS, through treatment with...

An Enhanced Immune Response of Mclk1+/− Mutant Mice Is Associated with Partial Protection from Fibrosis, Cancer and the Development of Biomarkers of Aging

The immune response is essential for survival by destroying microorganisms and pre-cancerous cells. However, inflammation, one aspect of this response, can result in short- and long-term deleterious side-effects. Mclk1+/− mutant mice can be long-lived despite displaying a hair-trigger inflammatory response and chronically activated macrophages as a result of high mitochondrial...

Mitochondrial Oxidative Stress Alters a Pathway in Caenorhabditis elegans Strongly Resembling That of Bile Acid Biosynthesis and Secretion in Vertebrates

Mammalian bile acids (BAs) are oxidized metabolites of cholesterol whose amphiphilic properties serve in lipid and cholesterol uptake. BAs also act as hormone-like substances that regulate metabolism. The Caenorhabditis elegans clk-1 mutants sustain elevated mitochondrial oxidative stress and display a slow defecation phenotype that is sensitive to the level of dietary...

Mclk1+/- mice are not resistant to the development of atherosclerosis

Background Mice with a single copy of Mclk1 (a.k.a. Coq7), a gene that encodes a mitochondrial enzyme required for the biosynthesis of ubiquinone and other functions, live longer than wild-type mice. The prolonged survival implies a decreased mortality from age-dependent lethal pathologies. Atherosclerosis is one of the main age-dependent pathologies in humans and can be modeled...

Deletion of the Mitochondrial Superoxide Dismutase sod-2 Extends Lifespan in Caenorhabditis elegans

The oxidative stress theory of aging postulates that aging results from the accumulation of molecular damage caused by reactive oxygen species (ROS) generated during normal metabolism. Superoxide dismutases (SODs) counteract this process by detoxifying superoxide. It has previously been shown that elimination of either cytoplasmic or mitochondrial SOD in yeast, flies, and mice...

CEP-1, the Caenorhabditis elegans p53 Homolog, Mediates Opposing Longevity Outcomes in Mitochondrial Electron Transport Chain Mutants

Caenorhabditis elegans CEP-1 and its mammalian homolog p53 are critical for responding to diverse stress signals. In this study, we found that cep-1 inactivation suppressed the prolonged lifespan of electron transport chain (ETC) mutants, such as isp-1 and nuo-6, but rescued the shortened lifespan of other ETC mutants, such as mev-1 and gas-1. We compared the CEP-1-regulated...

The C. elegans maternal-effect gene clk-2 is essential for embryonic development, encodes a protein homologous to yeast Tel2p and affects telomere length

McCright*,, Yue Zhang, Stephanie Felkai, Bernard Lakowski and Siegfried Hekimi SUMMARY The Caenorhabditis elegans maternal-effect clk genes are involved in the temporal control of development and behavior

Metazoan Scc4 Homologs Link Sister Chromatid Cohesion to Cell and Axon Migration Guidance

Saccharomyces cerevisiae Scc2 binds Scc4 to form an essential complex that loads cohesin onto chromosomes. The prevalence of Scc2 orthologs in eukaryotes emphasizes a conserved role in regulating sister chromatid cohesion, but homologs of Scc4 have not hitherto been identified outside certain fungi. Some metazoan orthologs of Scc2 were initially identified as developmental gene...