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DYSO

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Our group has a long experience in the study of organelles, and particularly mitochondria, under different aspects:


1- Study of the effects of mitochondria dysfunction

To study the impact of mitochondria dysfunction on cultured mammalian cells, we use different cell models presenting a mitochondrial dysfunction caused by chemical inhibitors of the electron transport chain (ETC), by uncoupling agents, by mitochondrial DNA (mtDNA) depletion (rho° cells) or by point mutations in mtDNA (such as MERRF or MELAS mutations) that impair the mitochondrial protein synthesis. We have mainly studied the impact of mitochondrial dysfunction on 3 types of cell responses: the retrograde signalling pathways, the apoptotic response and the metabolism in (pre)adipocytes.

 

2- Mitochondrial biogenesis during hepatogenic differentiation of human stem cells

A more recently developed research axis is devoted to investigate the link between mitochondria and cell differentiation, as mitochondrial biogenesis and metabolism have recently emerged as important actors of stemness and differentiation (Wanet et al, Stem Cells Dev 2015). We have first characterized the mitochondrial changes occurring during the hepatogenic differentiation of human bone marrow-mesenchymal stem cells (hBM-MSCs) and highlighted a strong mitochondrial biogenesis characterized by an increase in mitochondrial content, in mtDNA abundance, in several proteins of the ETC, and in OXPHOS activity, capacity and efficiency, accompanied by a net fragmentation of the mitochondrial network (Wanet et al, Int J Biochem Cell Biol 2014).

We currently study the molecular mechanisms underlying the interplay between mitochondrial biogenesis and BM-MSC hepatogenic differentiation.

3- Organelle cross-talk : a non lethal endoplasmic reticulum stress or a lysosomal dysfunction triggers mitochondria fragmentation

Evidence accumulated showing intimate physical and functional interactions between organelles such as lysosomes, the endoplasmic reticulum (ER) and mitochondria allowing exchange of calcium, lipids and metabolites. Read more ...

4. Mitochondria, obesity and insulin resistance : role of SIRT3 and miRNA differentially regulated by TNFa

Obesity is associated with increased adiposity and low-grade inflammation and oxidative stress in the white adipose tissues (WAT) in which TNFa and down-regulation of Sirtuin 3 (SIRT3), a mitochondrial deacetylase, plays a major role, respectively.  Read more ...

5. Mitochondria and intracellular bacteria

Brucella species are Gram-negative facultative intracellular bacteria responsible for a worldwide zoonotic disease known as brucellosis. Read more ...

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