Mitochondrial dynamics : from neurogenesis to neurodegeneration

Pascale BELENGUER

PR UPS
05 61 55 62 38

Team members

  Professor
  • Noélie DAVEZAC
  • Valérie MILS
  • Marie-Christine MIQUEL
  • Laetitia PELLOQUIN-ARNAUNE
  Technical staff
  • Marlène BOTELLA
  Postdoc
  • Macarena ARRAZOLA
  • Marion SZELECHOWSKI
  PhD
  • Nadège MERABET

Presentation

Mitochondria morphology varies according to cell type and cellular context from an interconnected filamentous network to isolated dots. This morphological plasticity depends on mitochondrial dynamics, a balance between antagonistic forces of fission and fusion. DRP1 and FIS1 control mitochondria outer membrane fission and mitofusins its fusion. Our team has identified one of the few known actors of inner membrane dynamics, OPA1, which mutations provoke an optic neuropathy (type 1 Dominant Optic Atrophy, ADOA-1).
During the last 5 years we focused our work on the molecular and functional characterization of OPA1 and of its yeast homologue Msp1, as well as on the pathophysiological mechanisms leading to ADOA-1. Mitochondrial dynamics influences the main functions of the organelle (respiration, calcium homeostasis, ROS production, apoptosis) and its distribution. Consequently, this phenomenon is due to play a major role in neurons because of their highly specialized nature and architecture as well as their plasticity during development and adulthood. A definite proof of the major role of mitochondrial dynamics in the nervous system came from the discovery that mutations in key actors of this process are responsible for neurodegenerative disorders.
While pursuing our investigations on the influence of mitochondrial dynamics, and of OPA1, on neurodegeneration, we start now to study the impact of mitochondrial dynamics on the functions and plasticity of mature and developing neurons.

 

Publications

  • Mils V, Bosch S, Roy J, Bel-Vialar S, Belenguer P, Pituello F, Miquel MC. .
    Mitochondrial reshaping accompanies neural differentiation in the developing spinal cord
    PLoS One
    2015 May 28;10(5):e0128130.
  • Millet A, Belenguer P, Davezac N..
    Method, process and kit for prognosis of OPA1 gene or OPA1 gene product deficit induced diseases
    European European Patent
    2014 Jan 14305448
  • Bertholet AM, Millet A, Guillermin O, Daloyau M, Davezac N, Miquel MC and Belenguer P.
    OPA1 loss affects neuronal maturation
    Brain
    2013 Jan 136:1518-33.
  • Magnifico S, Saias L, Deleglise B, Duplus E, Kilinc D, Miquel MC, Viovy JL, Brugg B, Peyrin JM.
    NAD acts on mitochondrial SirT3 to prevent axonal caspase activation and axonal degeneration
    FASEB J
    2013 Jan 27(12):4712-22.
  • Carneiro L, Allard C, Guissard C, Fioramonti X, Tourrel-Cuzin C, Bailbé D, Barreau C, Offer G, Nédelec E, Salin B, Rigoulet M, Belenguer P, Pénicaud L, Leloup C..
    Importance of Mitochondrial Dynamin-Related Protein 1 in Hypothalamic Glucose Sensitivity in Rats
    Antioxid Redox Signal
    2012 Jan 17:433-44.

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Université Paul Sabatier
118 Route de Narbonne

31062 TOULOUSE Cedex
France

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