LA RECHERCHE... THE RESEARCH...
Les mitochondries sont considérées comme la centrale énergétique des cellules en raison de leur rôle dans la phosphorylation oxydative et la production d'ATP, mais elles sont également impliquées dans d'autres processus physiologiques clés, notamment l'homéostasie du calcium, l'apoptose et la stéroïdogenèse. Les mitochondries forment des réseaux dans le cytosol qui sont constamment modifiés par des événements de fission et de fusion, un processus connu sous le nom de dynamique mitochondriale. Notre groupe étudie divers mécanismes par lesquels ces organites sont régulés et par lesquels ils sont impliqués dans le développement de conditions physiopathologiques.
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Mitochondria are considered as the cellular powerhouse due to their role in oxidative phosphorylation and ATP production, but they are also involved in other key physiological processes including calcium homeostasis, apoptosis and steroidogenesis. Mitochondria form networks into the cytosol which are constantly modified by fission and fusion events, a process known as mitochondrial dynamics. Our group studies various mechanisms by which these organelles are regulated and through which they are involved in the developement of pathophysiological conditions.
NOS PROJETS... OUR PROJECTS...
-Le rôle de la tyrosine kinase Src dans la physiologie et la dynamique mitochondriale
-La signalisation mitochondriale et les protéines G
-L'homéostasie mitochondriale dans la maladie de Parkinson
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-The tyrosine kinase Src in mitochondrial physiology and dynamics
-G protein signaling in mitochondria and behavior
-Mitochondrial homeostasis in Parkinson's disease
SRC KINASE AND MITOCHONDRIA
Src kinase is localized in several compartments within cells, including mitochondria. Our work has shown they can target several proteins to impact on mitochondrial physiology and dynamics (Guedouari et al 2021 Mitochondrion; Lurette et al 2022 Cell Mol Life Sci). Intramitochondrial Src affects mitochondrial functions in breast cancer cells to impact their aggressiveness (Djeungoue-Petga et al 2019 Cell Death and Disease). Src kinase also impacts on several steps of metabolism and appears involved in the ability to cope with food deprivation (Guedouari et al 2020 Cell Physiol Biochem). Our group continue to examine how Src-dependent signaling impacts on mitochondria and behavior.
G PROTEIN SIGNALING AND MITOCHONDRIA
Few G protein coupled receptors are localized within mitochondrial membranes. Our work has shown that the GPCR cannabinoid receptor CB1 is present in brain mitochondria where its activation affects brain metabolism and behavior (Bénard et al . 2012 Nat Neuro; Hebert-Chatelain 2016 Nature; Jimenez-Blasco et al 2020 Nature; Soria-Gomez et al 2021 Neuron). Our group generated specific tools to target and activate endogenous G proteins inside mitochondria and explore their role in brain metabolism and behavior.
MITOCHONDRIA IN PARKINSON'S DISEASE
Parkinson disease (PD) is a neurodegenerative movement disorder characterized by the loss of dopaminergic neurons. The main pathological hallmark of PD is accumulation of aggregated α-synuclein (α-syn) in cerebral tissue. Alterations of mitochondria have been observed in patients and several models of PD. However, the available models of PD used so far do not mimic appropriately the molecular events observed in PD. Our group developped specific tools to induce and control the aggregation of α-syn and accurately mimic PD and better understand the role of mitochondrial dysfunctions in the disease (Lurette et al 2023 Cell Death Dis).