Deciphering the interplay between mitochondrial dynamics and bioenergeticsConférence présentée par Arnaud Mourier

Le 31 mars 2025

Lundi 31 mars, 18h00

Bâtiment IBS-IRIS CHU Angers -  Salle de conférence, rez-de-chaussée.

Venez assister à la conférence : Deciphering the interplay between mitochondrial dynamics and bioenergetics présentée par Arnaud Mourier, Group Leader - BioDynaMit CNRS, Univ. Bordeaux, IBGC, UMR 5095.

Une conférence organisée dans le cadre d’un atelier technologique proposé par l’association meetochondrie, l’équipe Mitolab, le CHU d’Angers.

Deciphering the interplay between mitochondrial dynamics and bioenergetics

Mitochondria form a dynamic network within the cell as a result of balanced fusion and fission. In mammals, outer mitochondrial membrane fusion controls mitochondrial network morphology, promotes subcellular trafficking and ensures proper mitochondrial content mixing. This process is controlled by two homologous dynamin related proteins, MFN1 and MFN2, which are ubiquitously expressed across tissues. Intriguingly, in human, loss of function of MFN2 is responsible for the Charcot-Marie-Tooth type 2A neuropathy, whereas no pathogenic mutations are known in MFN1. Due to the poor understanding of the pathophysiological mechanisms underlying this neuropathy, there is currently no effective treatment to reverse or slow the disease process. In line with the clinical observations of CMT2A patients showing that loss of MFN2 function selectively affects neurons, transgenic KO mouse models show that loss of MFN1 in different tissues remains mostly aphenotypic, while loss of MFN2 is lethal only when the loss is targeted to the nervous system^1–3. During the past few years, our work characterizing of Mfn1 and Mfn2 knockout mice demonstrated that partial loss of fusion provoked by single Mfn2 KO could lead to isolated coenzyme Q loss⁴ whereas complete loss of fusion linked to double Mfn1 and Mfn2 KO was associated with combined loss of CoQ and severe loss of mitochondrial genome^5–7.

References

1.          Chen, H., McCaffery, J. M. & Chan, D. C. Mitochondrial Fusion Protects against Neurodegeneration in the Cerebellum. Cell 130, 548–562 (2007).

2.           Pham, A. H., Meng, S., Chu, Q. N. & Chan, D. C. Loss of Mfn2 results in progressive, retrograde degeneration of dopaminergic neurons in the nigrostriatal circuit. Human Molecular Genetics 21, 4817–4826 (2012).

3.           Lee, S. et al. Mitofusin 2 is necessary for striatal axonal projections of midbrain dopamine neurons. Hum. Mol. Genet. 21, 4827–4835 (2012).

4.           Mourier, A. et al. Mitofusin 2 is required to maintain mitochondrial coenzyme Q levels. J. Cell Biol. 208, 429–442 (2015).

5.           Silva Ramos, E., Larsson, N.-G. & Mourier, A. Bioenergetic roles of mitochondrial fusion. Biochim. Biophys. Acta 1857, 1277–1283 (2016).

6.           Silva Ramos, E. et al. Mitochondrial fusion is required for regulation of mitochondrial DNA replication. PLoS Genet. 15, e1008085 (2019).

7.           Chen, H. et al. Mitochondrial Fusion Is Required for mtDNA Stability in Skeletal Muscle and Tolerance of mtDNA Mutations. Cell 141, 280–289 (2010).