Monday, March 23, 2015

Fly model links mitochondrial function, cell death and heart disease

Martínez-Morentin L, Martínez L, Piloto S, Yang H, Schon EA, Garesse R, Bodmer R, Ocorr K, Cervera M, Arredondo JJ. Cardiac Deficiency of Single Cytochrome Oxidase Assembly Factor scox Induces p53 Dependent Apoptosis in a Drosophila Cardiomyopathy Model. Hum Mol Genet. 2015 Mar 19. pii: ddv106. PMID: 25792727.

From the abstract: "... most patients with mitochondrial disease produced by defects in the Oxidative Phosphorylation System (OXPHOS) are susceptible to cardiac involvement. ... One of the most frequent OXPHOS defect in humans frequently associated with cardiomyopathy is cytochrome c oxidase (COX) deficiency caused by mutations in COX assembly factors like Sco1 and Sco2. ... we have heart specifically interfered scox, the single Drosophila Sco orthologue. Cardiac-specific knockdown of scox reduces fly lifespan, and it severely compromises heart function and structure, producing dilated cardiomyopathy. ... Genetic and molecular evidence strongly suggests that dp53 is directly involved in the development of the cardiomyopathy induced by scox deficiency. Remarkably, apoptosis is enhanced in the muscle and liver of Sco2 knock-out mice, clearly suggesting that cell death is a key feature of the COX deficiencies produced by mutations in Sco genes in humans."

Tuesday, March 17, 2015

Epigenetic Signatures of Obesity — NEJM

Epigenetic Signatures of Obesity—NEJM

Epigenetics & Obesity

Öst A, Lempradl A, Casas E, Weigert M, Tiko T, Deniz M, Pantano L, Boenisch U, Itskov PM, Stoeckius M, Ruf M, Rajewsky N, Reuter G, Iovino N, Ribeiro C, Alenius M, Heyne S, Vavouri T, Pospisilik JA. Paternal diet defines offspring chromatin state and intergenerational obesity. Cell. 2014 Dec 4;159(6):1352-64. PMID: 25480298.

From the abstract:  "... We present a Drosophila model of paternal-diet-induced intergenerational metabolic reprogramming (IGMR) and identify genes required for its encoding in offspring. ... Critically, we find evidence that a similar system may regulate obesity susceptibility and phenotype variation in mice and humans. The findings provide insight into the mechanisms underlying intergenerational metabolic reprogramming and carry profound implications for our understanding of phenotypic variation and evolution."

See also: Ozanne SE. Epigenetic signatures of obesity. N Engl J Med. 2015 Mar 5;372(10):973-4. PMID: 25738675.

Monday, March 2, 2015

Review of fly models of mitochondrial diseases

Foriel S, Willems P, Smeitink J, Schenck A, Beyrath J. Mitochondrial diseases: Drosophila melanogaster as a model to evaluate potential therapeutics. Int J Biochem Cell Biol. 2015 Feb 7. pii: S1357-2725(15)00034-5. PMID: 25666557.

From the abstract: "... mitochondrial diseases comprise a wide range of clinical, biochemical and genetic heterogeneous disorders. ... Despite intense research efforts, patients are still without effective treatment. ... Here, we review existing Drosophila melanogaster models for mitochondrial diseases, with a focus on alterations in oxidative phosphorylation, and discuss the potential of this powerful model organism in the process of drug target discovery."

FlyRNAi: Primary cell screen performed at DRSC explores aut...

FlyRNAi: Primary cell screen performed at DRSC explores aut...: Zirin J, Nieuwenhuis J, Samsonova A, Tao R, Perrimon N. Regulators of autophagosome formation in Drosophila muscles. PLoS Genet. 2015 Feb 1...

Drosophila used to help characterize a newly identified mutation in FMRP associated with Fragile X syndrome

Okray Z, de Esch CE, Van Esch H, Devriendt K, Claeys A, Yan J, Verbeeck J, Froyen G, Willemsen R, de Vrij FM, Hassan BA. A novel fragile X syndrome mutation reveals a conserved role for the carboxy-terminus in FMRP localization and function. EMBO Mol Med. 2015 Feb 17. pii: e201404576. PMID: 25693964.

From the abstract: "... In vivo analyses in Drosophila demonstrate that a patient-mimetic mutation alters the localization and function of Dfmrp in neurons, leading to neomorphic neuronal phenotypes."