14 research outputs found
Mitochondrial dynamics and disease, OPA1
AbstractThe mitochondria are dynamic organelles that constantly fuse and divide. An equilibrium between fusion and fission controls the morphology of the mitochondria, which appear as dots or elongated tubules depending the prevailing force. Characterization of the components of the fission and fusion machineries has progressed considerably, and the emerging question now is what role mitochondrial dynamics play in mitochondrial and cellular functions. Its importance has been highlighted by the discovery that two human diseases are caused by mutations in the two mitochondrial pro-fusion genes, MFN2 and OPA1. This review will focus on data concerning the function of OPA1, mutations in which cause optic atrophy, with respect to the underlying pathophysiological processes
Specific interaction between 14-3-3 isoforms and the human CDC25B phosphatase
International audienc
Mitochondrial Reshaping Accompanies Neural Differentiation in the Developing Spinal Cord
International audienceMitochondria, long known as the cell powerhouses, also regulate redox signaling and arbitrate cell survival. The organelles are now appreciated to exert additional critical roles in cell state transition from a pluripotent to a differentiated state through balancing glycolytic and respiratory metabolism. These metabolic adaptations were recently shown to be concomi-tant with mitochondrial morphology changes and are thus possibly regulated by contingencies of mitochondrial dynamics. In this context, we examined, for the first time, mitochondrial network plasticity during the transition from proliferating neural progenitors to post-mitotic differentiating neurons. We found that mitochondria underwent morphological reshaping in the developing neural tube of chick and mouse embryos. In the proliferating population, mitochondria in the mitotic cells lying at the apical side were very small and round, while they appeared thick and short in interphase cells. In differentiating neurons, mi-tochondria were reorganized into a thin, dense network. This reshaping of the mitochondrial network was not specific of a subtype of progenitors or neurons, suggesting that this is a general event accompanying neurogenesis in the spinal cord. Our data shed new light on the various changes occurring in the mitochondrial network during neurogenesis and suggest that mitochondrial dynamics could play a role in the neurogenic process
Immunodetection of the outer mitochondrial membranes TOM20 reveals the same changes in mitochondrial morphology than OXPHOS.
<p>Panels A to C represent confocal micrographs of TOM20 (red) and OXPHOS (green) mitochondria staining in cross-sections of the spinal cord of E3.5 chick embryo. Panel A is a low magnification indicative of the enlargement positions shown in B (left) and C (right). In panel B neural progenitors display short and thick labeled-mitochondria (black and white). In panel C differentiating neurons show a longer and denser mitochondrial network (red or green). Note the evident overlay of the two red and green stainings (left panels). Scale bars, 20ÎĽm. Panel D illustrates the TOM20-labeled very small and round mitochondria (red) observed in mitotic cells (white arrows) stained with MPM2 antibody (green). Scale bars, 20ÎĽm.</p
Differential expression of effectors of mitochondrial dynamics in E1.5 and E3.5 chicken neural tube extracts.
<p>Representative immunoblot showing the expression of the mitochondrial dynamics proteins, DRP1, MFN2 and OPA1, as well as mitochondrial respiratory complexes V, III and II and HSP60 protein in E1.5 and E3.5 chicken neural tubes extracts, with actin used as control. While DRP1 and MFN2 are represented as single bands of similar intensities at both ages, staining of the OPA1 isoforms reveals an increase in the longest isoform in the E3.5 extract compared with the E1.5 extract.</p
Mitochondrial reshaping accompanies neural progenitor differentiation in the mouse neural tube.
<p>Panels A to C represent confocal micrographs of green ATP synthase-stained mitochondria in E9.5–10 neural tube transverse sections (scale bar 50 μm), magnified in the mid- and right-side panels (scale bar 10 μm). In panel A, Olig2-stained neuronal progenitors (blue), future motor neurons, contain short and thick mitochondria. In panel B, beta3-tubulin-stained (purple) differentiating neurons are endowed with a longer and denser mitochondrial network. In panel C, P-H3-stained (blue) mitotic progenitors are shown to contain very small and round mitochondria.</p
The OXPHOS antibody labels respiratory complex proteins in Western blots and immunocytochemical experiments.
<p>(A) Representative immunoblot of OXPHOS antibody labeling, showing the expected 5 proteins in HeLa cells extracts, and proteins from the V, III, and II complexes in chicken DF1 fibroblasts. (B) Fluorescent micrographs of OXPHOS labeling showing green filamentous mitochondria in HeLa cells (upper left panel) and chick DF1 fibroblasts (lower left panel). MitoTracker staining of DF1 cells depicts a red mitochondrial network (lower right panel) superimposed on the green OXPHOS staining (upper right panel) (scale bar 10 ÎĽm). (C) Confocal micrograph of a transversal section from a E3.5 chicken neural tube showing OXPHOS-immunostained mitochondria (green) and a mosaic staining of Mito-DsRed-labeled mitochondria on the left side (red) (scale bar 50 ÎĽm). Higher magnification at the level of the ventricular zone illustrates the co-localization of the Mito-DsRed (red) and OXPHOS staining (green) (scale bar, 20 ÎĽm).</p
Mitochondrial reshaping accompanies neuronal differentiation in the chicken neural tube.
<p>Panels A through E represent confocal micrographs of green OXPHOS-stained mitochondria in E3.5 transversal sections (scale bar 50 ÎĽm), magnified in the mid- and right-side panels (scale bar 10 ÎĽm). In panels A, C, and E, SR101-Phalloidin signaling (red) was used to mark the cellular contours. Neuronal progenitors, immunolabeled either with Olig2 for future motor neurons (A, blue) or Pax6 for future interneurons (C, blue), contain short and thick mitochondria. In panel B, JC7-immunodetection (purple) delineates the surface of differentiating motor neurons endowed with a longer and denser mitochondrial network. In panel D, the mitochondrial network of beta3-tubulin-stained differentiating neurons (purple) is also long and dense. In panel E, P-H3-immunostained (blue) mitotic progenitors are shown to contain very small and round mitochondria.</p