<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Ghezzi, Daniele</style></author><author><style face="normal" font="default" size="100%">Arzuffi, Paola</style></author><author><style face="normal" font="default" size="100%">Zordan, Mauro</style></author><author><style face="normal" font="default" size="100%">Da Re, Caterina</style></author><author><style face="normal" font="default" size="100%">Lamperti, Costanza</style></author><author><style face="normal" font="default" size="100%">Benna, Clara</style></author><author><style face="normal" font="default" size="100%">d'Adamo, Pio</style></author><author><style face="normal" font="default" size="100%">Diodato, Daria</style></author><author><style face="normal" font="default" size="100%">Costa, Rodolfo</style></author><author><style face="normal" font="default" size="100%">Mariotti, Caterina</style></author><author><style face="normal" font="default" size="100%">Uziel, Graziella</style></author><author><style face="normal" font="default" size="100%">Smiderle, Cristina</style></author><author><style face="normal" font="default" size="100%">Zeviani, Massimo</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Mutations in TTC19 cause mitochondrial complex III deficiency and neurological impairment in humans and flies.</style></title><secondary-title><style face="normal" font="default" size="100%">Nat Genet</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Nat. Genet.</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Adult</style></keyword><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Brain</style></keyword><keyword><style  face="normal" font="default" size="100%">Codon, Nonsense</style></keyword><keyword><style  face="normal" font="default" size="100%">Drosophila melanogaster</style></keyword><keyword><style  face="normal" font="default" size="100%">Electron Transport Complex III</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Gene Knockdown Techniques</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Membrane Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Mitochondria</style></keyword><keyword><style  face="normal" font="default" size="100%">Mitochondrial Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Nervous System Diseases</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2011</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2011 Mar</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">43</style></volume><pages><style face="normal" font="default" size="100%">259-63</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Although mutations in CYTB (cytochrome b) or BCS1L have been reported in isolated defects of mitochondrial respiratory chain complex III (cIII), most cIII-defective individuals remain genetically undefined. We identified a homozygous nonsense mutation in the gene encoding tetratricopeptide 19 (TTC19) in individuals from two families affected by progressive encephalopathy associated with profound cIII deficiency and accumulation of cIII-specific assembly intermediates. We later found a second homozygous nonsense mutation in a fourth affected individual. We demonstrated that TTC19 is embedded in the inner mitochondrial membrane as part of two high-molecular-weight complexes, one of which coincides with cIII. We then showed a physical interaction between TTC19 and cIII by coimmunoprecipitation. We also investigated a Drosophila melanogaster knockout model for TTC19 that showed low fertility, adult-onset locomotor impairment and bang sensitivity, associated with cIII deficiency. TTC19 is a putative cIII assembly factor whose disruption is associated with severe neurological abnormalities in humans and flies.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">3</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/21278747?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Ghezzi, Daniele</style></author><author><style face="normal" font="default" size="100%">Sevrioukova, Irina</style></author><author><style face="normal" font="default" size="100%">Invernizzi, Federica</style></author><author><style face="normal" font="default" size="100%">Lamperti, Costanza</style></author><author><style face="normal" font="default" size="100%">Mora, Marina</style></author><author><style face="normal" font="default" size="100%">d'Adamo, Pio</style></author><author><style face="normal" font="default" size="100%">Novara, Francesca</style></author><author><style face="normal" font="default" size="100%">Zuffardi, Orsetta</style></author><author><style face="normal" font="default" size="100%">Uziel, Graziella</style></author><author><style face="normal" font="default" size="100%">Zeviani, Massimo</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Severe X-linked mitochondrial encephalomyopathy associated with a mutation in apoptosis-inducing factor.</style></title><secondary-title><style face="normal" font="default" size="100%">Am J Hum Genet</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Am. J. Hum. Genet.</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Apoptosis</style></keyword><keyword><style  face="normal" font="default" size="100%">Apoptosis Inducing Factor</style></keyword><keyword><style  face="normal" font="default" size="100%">Caspase 3</style></keyword><keyword><style  face="normal" font="default" size="100%">Computer Simulation</style></keyword><keyword><style  face="normal" font="default" size="100%">Dietary Supplements</style></keyword><keyword><style  face="normal" font="default" size="100%">DNA Primers</style></keyword><keyword><style  face="normal" font="default" size="100%">DNA, Mitochondrial</style></keyword><keyword><style  face="normal" font="default" size="100%">Electron Transport</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Fibroblasts</style></keyword><keyword><style  face="normal" font="default" size="100%">Flavin-Adenine Dinucleotide</style></keyword><keyword><style  face="normal" font="default" size="100%">Genes, X-Linked</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">In Situ Nick-End Labeling</style></keyword><keyword><style  face="normal" font="default" size="100%">Infant, Newborn</style></keyword><keyword><style  face="normal" font="default" size="100%">Magnetic Resonance Imaging</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Mitochondrial Encephalomyopathies</style></keyword><keyword><style  face="normal" font="default" size="100%">Muscle, Skeletal</style></keyword><keyword><style  face="normal" font="default" size="100%">Mutation</style></keyword><keyword><style  face="normal" font="default" size="100%">Nervous System Diseases</style></keyword><keyword><style  face="normal" font="default" size="100%">Pedigree</style></keyword><keyword><style  face="normal" font="default" size="100%">Poly(ADP-ribose) Polymerases</style></keyword><keyword><style  face="normal" font="default" size="100%">Protein Conformation</style></keyword><keyword><style  face="normal" font="default" size="100%">Riboflavin</style></keyword><keyword><style  face="normal" font="default" size="100%">Staurosporine</style></keyword><keyword><style  face="normal" font="default" size="100%">Twins, Monozygotic</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2010</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2010 Apr 9</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">86</style></volume><pages><style face="normal" font="default" size="100%">639-49</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;We investigated two male infant patients who were given a diagnosis of progressive mitochondrial encephalomyopathy on the basis of clinical, biochemical, and morphological features. These patients were born from monozygotic twin sisters and unrelated fathers, suggesting an X-linked trait. Fibroblasts from both showed reduction of respiratory chain (RC) cIII and cIV, but not of cI activities. We found a disease-segregating mutation in the X-linked AIFM1 gene, encoding the Apoptosis-Inducing Factor (AIF) mitochondrion-associated 1 precursor that deletes arginine 201 (R201 del). Under normal conditions, mature AIF is a FAD-dependent NADH oxidase of unknown function and is targeted to the mitochondrial intermembrane space (this form is called AIF(mit)). Upon apoptogenic stimuli, a soluble form (AIF(sol)) is released by proteolytic cleavage and migrates to the nucleus, where it induces &quot;parthanatos,&quot; i.e., caspase-independent fragmentation of chromosomal DNA. In vitro, the AIF(R201 del) mutation decreases stability of both AIF(mit) and AIF(sol) and increases the AIF(sol) DNA binding affinity, a prerequisite for nuclear apoptosis. In AIF(R201 del) fibroblasts, staurosporine-induced parthanatos was markedly increased, whereas re-expression of AIF(wt) induced recovery of RC activities. Numerous TUNEL-positive, caspase 3-negative nuclei were visualized in patient #1's muscle, again indicating markedly increased parthanatos in the AIF(R201 del) critical tissues. We conclude that AIF(R201 del) is an unstable mutant variant associated with increased parthanatos-linked cell death. Our data suggest a role for AIF in RC integrity and mtDNA maintenance, at least in some tissues. Interestingly, riboflavin supplementation was associated with prolonged improvement of patient #1's neurological conditions, as well as correction of RC defects in mutant fibroblasts, suggesting that stabilization of the FAD binding in AIF(mit) is beneficial.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">4</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/20362274?dopt=Abstract</style></custom1></record></records></xml>