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Research > Team Bioenergetics and dynamics of mitochondria

Bioenergetics and dynamics of mitochondria

Principal Investigator : Arnaud Mourier

Bandeau Biodynamit

Team Members

Jordan Cougouilles - Étudiant Master 2

Elodie Cougouilles - CDD AI CNRS

Thomas Daubon - CRCN CNRS

Claudine David - IEHC CNRS

Thibaut Molinié - Doctorant MESR

Arnaud Mourier - CRCN CNRS

Preslia Okou - Etudiante Master 2

Manuel Rojo - DR2 CNRS

Irati Romero-Garmendia - Post-Doctorante

Gro Vatne Rosland - Post-Doctorante invitée

 

Former Team Members

Rech Giovana - Doctorante visiteuse Celia Fernandez-Sanz - Post-Doctorante IdEX Bordeaux
Julian Perrin - Etudiant Master 2 Esra Karatas - Etudiante Master 2

 

Summary

Mitochondria are double membrane organelles, which hold a central role in cell metabolism as they produce the bulk part of the energy currency ATP through the oxidative phosphorylation (OXPHOS) system. Beside their role in energy transduction, mitochondria are also involved in some intermediary metabolism pathways, Calcium homeostasis, cell behavior, and apoptosis. Mitochondrial dysfunction is a common cause of disease in both children and adults. Due to their key energetic role, the localization of mitochondria at intracellular sites of high-energy demand is crucial to maintain cell energy metabolism. In muscle, mitochondria are embedded between myofibrils that consume ATP during contraction. Likewise, in neurons, mitochondria are transported and accumulate in synapses to provide the energy required to maintain and regulate neurotransmission.

Their intracellular distribution depends on their mobility and their highly plastic morphology, which results from balanced fusion and fission processes. Beyond its role in maintaining proper mitochondrial morphology and subcellular location, mitochondrial dynamics is key to maintain mitochondrial genome, which is essential to ensure proper OXPHOS assembly and activity.

During the past two decades, a significant amount of relevant data has been obtained on the proteins involved in mitochondrial fusion/fission dynamics, notably several dynamin related proteins (DRPs: DRP1, OPA1, MFN1, MFN2). Interestingly, pathogenic mutations in OPA1 and MFN2 cause neuropathies ranging from mild to severe form, causing dominant optic atrophy or peripheral neuropathies as Charcot-Marie-Tooth (CMT) type 2A disease. The pathological spectrum associated with disturbed mitochondrial dynamics has recently expanded to include Parkinson's, Huntington's and Alzheimer's diseases. Pathogenic mutations involved in Parkinson's and Huntington's diseases have been associated with an excessive mitochondrial fragmentation.

Recently, Thomas Daubon joined us as permanent researcher for developing a topic based on "intracellular energy metabolism rewiring and intercellular metabolic communication in Glioblastoma". The main long-term objective of this research axis is to characterize metabolic coupling between glioma cells and neurons or immune cells and determine its importance for glioblastoma development (mitochondrial respiration and lactate fermentation).

 

Research Activity

Scientific goals of the BioDynaMit group

 

Image Biodynamit 1

 

Skills and expertise

Mitochondrial dynamics: We have several tools allowing visualising and characterizing mitochondrial morphology and evaluating mitochondrial dynamic activity. We also develop new tools to investigate inter-organelar communication.

Mitochondrial bioenergetics: The lab is equipped with last generation Oroboros oxygraph O2K instruments, fluorimeter and spectrophotometer allowing proper and accurate characterization of cellular and mitochondrial bioenergetics properties. To this end we assess oxygen consumption of cells, permeabilized cells or isolated mitochondria; mitochondrial membrane potential, ATP production, ROS production rate and enzyme activity and content of OXPHOS system. We also characterize the supramolecular organization of the OXPHOS system by BN-PAGE (Blue Native Polyacrylamide Gels)

Cell behaviors: 3D cell invasion from spheroids, cell migration, proliferation, automated analysis

Patient-derived xenografts: intracranial implantation of glioblastoma stem-like cells into immunodeficient animals, pharmacological treatments, local irradiation. Skills in immunohistology from frozen sections. Close relation with bioinfomaticians for in vivo RNAseq and proteomics analysis.

 

Active Collaborations

National International

 

Keywords

Energy metabolism - Bioenergetics - Mitochondrial dynamics - DRP1 - OPA1 - MFN1 - MFN2 - CMT2A - DOA - Glioblastoma - invasion - therapy - metabolic symbiosis - lactate

 

Complete Bibliography

https://www.ncbi.nlm.nih.gov/myncbi/browse/collection/55318450

 

Selected publications

Séité S, Mourier A, Camougrand N, Salin B, Figueiredo-Silva AC, Fontagné-Dicharry S, Panserat S, Seiliez I. Dietary methionine deficiency affects oxidative status, mitochondrial integrity and mitophagy in the liver of rainbow trout (Oncorhynchus mykiss). Sci Rep. 2018 Jul 5;8(1):10151

Brandt T, Mourier A, Tain LS, Partridge L, Larsson NG, Kühlbrandt W. Changes of mitochondrial ultrastructure and function during ageing in mice and <i>Drosophila</i>. Elife. 2017 Jul 12;6

Mourier A, Motori E, Brandt T, Lagouge M, Atanassov I, Galinier A, Rappl G, Brodesser S, Hultenby K, Dieterich C, Larsson NG. Mitofusin 2 is required to maintain mitochondrial coenzyme Q levels. J Cell Biol. 2015 Feb 16;208(4):429-42

Mourier A, Matic S, Ruzzenente B, Larsson NG, Milenkovic D. The respiratory chain supercomplex organization is independent of COX7a2l isoforms. Cell Metab. 2014 Dec 2;20(6):1069-75

Sauvanet C, Duvezin-Caubet S, Salin B, David C, Massoni-Laporte A, di Rago JP, Rojo M. Mitochondrial DNA mutations provoke dominant inhibition of mitochondrial inner membrane fusion. PLoS One. 2012;7(11):e49639

 

Financial Support

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