Mitochondrial dynamics: quantifying mitochondrial fusion in vitro

Mitochondrial fusion is an essential process for preserving the integrity and stability of mitochondrial DNA; however, regulation of this process remains largely mysterious. In this issue of BMC Biology, Schauss and colleagues describe a simple, reliable, and robust novel assay that allows fusion of mammalian mitochondria to be quantified in vitro

The FASTK family of proteins: emerging regulators of mitochondrial RNA biology

Abstract The FASTK family proteins have recently emerged as key post-transcriptional regulators of mitochondrial gene expression. FASTK, the founding member and its homologs FASTKD1–5 are architecturally related RNA-binding proteins, each having a different function in the regulation of mitochondrial RNA biology, from mRNA processing and maturation to ribosome assembly and translation. In this review, we outline the structure, evolution and function of these FASTK proteins and discuss the individual role that each has in mitochondrial RNA biology. In addition, we highlight the aspects of FASTK research that still require more attention

A human mitochondrial poly(A) polymerase mutation reveals the complexities of post-transcriptional mitochondrial gene expression

The p.N478D missense mutation in human mitochondrial poly(A) polymerase (mtPAP) has previously been implicated in a form of spastic ataxia with optic atrophy. In this study, we have investigated fibroblast cell lines established from family members. The homozygous mutation resulted in the loss of polyadenylation of all mitochondrial transcripts assessed; however, oligoadenylation was retained. Interestingly, this had differential effects on transcript stability that were dependent on the particular species of transcript. These changes were accompanied by a severe loss of oxidative phosphorylation complexes I and IV, and perturbation of de novo mitochondrial protein synthesis. Decreases in transcript polyadenylation and in respiratory chain complexes were effectively rescued by overexpression of wild-type mtPAP. Both mutated and wild-type mtPAP localized to the mitochondrial RNA-processing granules thereby eliminating mislocalization as a cause of defective polyadenylation. In vitro polyadenylation assays revealed severely compromised activity by the mutated protein, which generated only short oligo(A) extensions on RNA substrates, irrespective of RNA secondary structure. The addition of LRPPRC/SLIRP, a mitochondrial RNA-binding complex, enhanced activity of the wild-type mtPAP resulting in increased overall tail length. The LRPPRC/SLIRP effect although present was less marked with mutated mtPAP, independent of RNA secondary structure. We conclude that (i) the polymerase activity of mtPAP can be modulated by the presence of LRPPRC/SLIRP, (ii) N478D mtPAP mutation decreases polymerase activity and (iii) the alteration in poly(A) length is sufficient to cause dysregulation of post-transcriptional expression and the pathogenic lack of respiratory chain complexe

Pion production and charged-particle multiplicity selection in relativistic nuclear collisions

Spectra of positive pions with energies of 15-95 MeV were measured for high energy proton, 4He, 20Ne, and 40Ar bombardments of targets of 27Al, 40Ca, 107,109Ag, 197Au, and 238U. A Si-Ge telescope was used to identify charged pions by dE / dx-E and, in addition, stopped pi + were tagged by the subsequent muon decay. In all, results for 14 target-projectile combinations are presented to study the dependence of pion emission patterns on the bombarding energy (from E / A=0.25 to 2.1 GeV) and on the target and the projectile masses. In addition, associated charged-particle multiplicities were measured in an 80-paddle array of plastic scintillators, and used to make impact parameter selections on the pion-inclusive data. NUCLEAR REACTIONS U(20Ne, pi +), E / A=250 MeV; U(40Ar, pi +), Ca(40Ar, pi +), U(20Ne, pi +), Au(20Ne, pi +), Ag(20Ne, pi +), Al(20Ne, pi +), U(4He, pi +), Al(4He, pi +). E / A=400 MeV; Ca(40Ar, pi +), U(20Ne, pi +), U(4He, pi +), U(p, pi +), E / A=1.05), GeV; U(20Ne, pi +), E / A=2.1 GeV; measured sigma (E, theta ), inclusive and selected on associated charged-particle multiplicity

Spectra of p, d, and t from relativistic nuclear collisions

Inclusive energy spectra of protons, deuterons, and tritons were measured with a telescope of silicon and germanium detectors with a detection range for proton energies up to 200 MeV. Fifteen sets of data were taken using projectiles ranging from protons to 40Ar on targets from 27Al to 238U at bombarding energies from 240 MeV/nucleon to 2.1 GeV/nucleon. Particular attention was paid to the absolute normalization of the cross sections. For three previously reported reactions, He fragment cross sections have been corrected and are presented. To facilitate a comparison with theory the sum of nucleonic charges emitted as protons plus composite particles was estimated and is presented as a function of fragment energy per nucleon in the interval from 15 to 200 MeV/nucleon. For low-energy fragments at forward angles the protons account for only 25% of the nucleonic charges. The equal mass 40Ar plus Ca systems were examined in the center of mass. Here at 0.4 GeV/nucleon 40Ar plus Ca the proton spectra appear to be nearly isotropic in the center of mass over the region measured. Comparisons of some data with firestreak, cascade, and fluid dynamics models indicate a failure of the first and a fair agreement with the latter two. In addition, associated fast charged particle multiplicities (where the particles had energies larger than 25 MeV/nucleon) and azimuthal correlations were measured with an 80 counter array of plastic scintillators. It was found that the associated multiplicities were a smooth function of the total kinetic energy of the projectile. NUCLEAR REACTIONS U(20Ne,X), E / A=240 MeV/nucleon; U(40Ar,X), Ca(40Ar,X), U(20Ne,X), Au(20Ne,X), Ag(20Ne,X), Al(20Ne,X), U(4He,X), Al(4He,X), E / A=390 MeV/nucleon; U(40Ar,X), Ca(40Ar,X), U(20Ne,X), U(4He,X), U(p,X), E / A=1.04 GeV/nucleon; U(20Ne,X), E / A=2.1 GeV/nucleon; measured sigma (E, theta ), X=p,d,t

Excitation of the Delta (1232)-Resonance in Proton-Nucleus Collisions

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A mitochondria-specific isoform of FASTK is present in mitochondrial RNA granules and regulates gene expression and function

Under a Creative Commons license.-- et al.The mitochondrial genome relies heavily on post-transcriptional events for its proper expression, and misregulation of this process can cause mitochondrial genetic diseases in humans. Here, we report that a novel translational variant of Fas-activated serine/threonine kinase (FASTK) co-localizes with mitochondrial RNA granules and is required for the biogenesis of ND6 mRNA, a mitochondrial-encoded subunit of the NADH dehydrogenase complex (complex I). We show that ablating FASTK expression in cultured cells and mice results specifically in loss of ND6 mRNA and reduced complex I activity in vivo. FASTK binds at multiple sites along the ND6 mRNA and its precursors and cooperates with the mitochondrial degradosome to ensure regulated ND6 mRNA biogenesis. These data provide insights into the mechanism and control of mitochondrial RNA processing within mitochondrial RNA granules.This work was supported by the Swiss National Science Foundation (31993A-141068/1), IGE3, and the State of Geneva. MS work was supported by the Gerencia Regional de Salud de la JCyL (GRS 642/A/11) and Roche Diagnostics.Peer Reviewe

Les principales mesures des trente dernières années dans le secteur curatif

International audiencePendant ces trente dernières années le système de soins curatifs a été profondément transformé. Les politiques publiques se sont données pour objectif de le centraliser, le régionaliser et le transformer par décret, l'organiser par territoire, le globaliser, le coordonner, l'organiser en parcours de soins…. Avec des résultats variables