Research topics

Research / expertise topics

Three fundamental strategies and thematics are developed :

1) mitochondrial dynamics,

2) maintenance of mitochondrial genome integrity,

3) mitochondrial metabolism

With respect to hereditary and common mitochondrial diseases:

1) Dominant Optic Atrophy, Charcot Marie Tooth disease, encephalopathies, and myopathies, myocardial infarction, arterial hypertension,

2) Mitochondrial DNA depletion syndromes, progressive external ophthalmoplegia and ovarian failure, intrauterine growth retardation,

3) Leber Hereditary Optic Neuropathy, MELAS, Leigh Syndrome, Glaucoma, DMLA, Myopia, Thyroid and Kidney Cancer, Sickle Cell Disease, Endometriosis, Forensic medicine.

Know-how

Service delivery

Energetic properties and cell metabolism :

Oxygraphy :

The laboratory is equipped with a high-precision oxygraph allowing the analysis of oxygen concentration and flow (Oroboros).

MitoLab is aslox equipped of Seahorse XF Analyzers measure oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) of live cells in a multi-well plate

Measurement of maximal activity of complexes :

The analysis of the maximal activity of each complex of the respiratory chain (complexes I to IV), of ATPsynthase and the enzymes of the Krebs cycle or beta-oxidation, is carried out by spectrophotometry, on isolated mitochondria, cells, or tissue homogenates. 

Mitochondrial complexes and supercomplexes structure :

Western-blot :

Western blot analysis can be used to target specific protéins subunits of interest. The laboratory is equipped of Li-Cor oddisey Fc technology to read the protein on the membrane. 

BN-Page :

Mitochondrial complexes are multi-subunits enzymes formed of up to ≈ 50 subunits (complexe I). Complexes expression and or assembly are commobnly analyzed using Blue-Native electrophoresis. This method alos enable to study the composition of the super-structure (supercomplex) of the respiratory chain. 
Native PAGE separations are run in non-denaturing conditions. We used alsow the  Li-Cor oddisey Fc technology to read membrane.

Mitochondrial DNA genetic analysis : 

Mt DNA sequencing / haplotyping quantification qPCR :

Click here to have more informations

qPCR:

Modifications of respiratory chain functioning can also be linked to a variation in mtDNA copy number, even a decrease (depletion) or and increase (mitochondrial biogenesis). This can be evaluated by quantitative PCR by establishing a ratio between a mtDNA encoded gene and a nuclear encoded one.

Mitochondrial dynamics imaging 

We first use the Metamorph® software for image processing, morphometry and mitochondrial measurements of motility (Chevrollier et al., 2008; Cassereau et al. 2009). By using Imaris 7.1.1® software (Bitplane, Zurich, Switzerland) we increase the analysis level by a 3D processing.This technique allows the determination of mitochondrial length, volume, number of connections per cell, the nucleoids distribution within the cells and the mitochondrial membrane potential. 

Bioinformatics analysis of the mitochondrial proteome and the mutational spectrum :

We compared in silico sequences of human mitochondrial proteins with those of prokaryotes and showed that most of the proteins involved in such diseases are homologous to prokaryotic proteins. We then developed a bioinformatics research strategy to identify new mitochondrial proteins on the basis of their prokaryotic origin and the presence of a characteristic N-terminal extension. All known prokaryotic proteomes were compared to the human genome and various filtering tools were developed to identify new proteins.

Partnerships

Industrial partnerships

Publications involving CARFI  technology:

• INSERM, Université de Bordeaux : Lhomme A, Gilbert G, Pele T, Deweirdt J, Henrion D, Baudrimont I, Campagnac M, Marthan R, Guibert C, Ducret T, Savineau JP, Quignard JF. Stretch-activated Piezo1 Channel in Endothelial Cells Relaxes Mouse Intrapulmonary Arteries. Am J Respir Cell Mol Biol. 2019 Jun;60(6):650-658.
• CNRS, Université de Lorraine: Meyer M, Foulquier S, Dupuis F, Flament S, Grimaud L, Henrion D, Lartaud I, Monard G, Grillier-Vuissoz I, Boisbrun M. Synthesis and evaluation of new designed multiple ligands directed towards both peroxisome proliferator-activated receptor-γ and angiotensin II type 1 receptor. Eur J Med Chem. 2018 Aug 31;158:334-352.INRA, Angers : Schinkovitz A, Le Pogam P, Derbré S, Vessieres E, Blanchard P, Thirumaran SL, Breard D, Aumond MC, Zehl M, Urban E, Kaur A, Jäger N, Hofer S, Kopp B, Stuppner H, Baglin I, Seraphin D, Tomasi S, Henrion D, Boustie J, Richomme P. Secondary metabolites from lichen as potent inhibitors of advanced glycation end products and vasodilative agents. Fitoterapia. 2018 Oct 16. pii: S0367-326X(18)31363-7.
• CHU, Angers : Urbanski G, Caillon A, Poli C, Kauffenstein G, Begorre MA, Loufrani L, Henrion D, Belizna C. Hydroxychloroquine partially prevents endothelial dysfunction induced by anti-beta-2-GPI antibodies in an in vivo mouse model of antiphospholipid syndrome. PLoS One. 2018; 13(11):e0206814.
• SCRIPPS Institute, San Diego, Californie, USA: Xu J, Mathur J, Vessières V, Hammack S, Nonomura K, Favre J, Grimaud L, Petrus M, Francisco A, Li J, Lee V, Xiang FL, Mainquist JK, Cahalan SM, Orth AP, Walker JR, Ma S, Lukacs V, Bandell M, Bordone L, Laffitte B, Xu Y, Chien S, Henrion D and Patapoutian A. GPR68 is a sensor of shear stress in endothelial cells of small-diameter arteries and regulates flow-mediated dilation and remodeling. Cell 2018;173(3):762-775.
• CHU, Angers : Rineau E, Gaillard T, Gueguen N, Procaccio V, Henrion D, Prunier F, Lasocki S. Iron deficiency without anemia is responsible for decreased left ventricular function and reduced mitochondrial complex I activity in a mouse model. Int J Cardiol. 2018;266:206-212
• INSERM, PARCC, Paris : Merkulova-Rainon T, Mantsounga CS, Broquères-You D, Pinto C, Vilar J, Cifuentes D, Bonnin P, Kubis N, Henrion D, Silvestre JS, Lévy BI. Peripheral post-ischemic vascular repair is impaired in a murine model of Alzheimer's disease. Angiogenesis. 2018. doi: 10.1007/s10456-018-9608-7
• INSERM, Université de Toulouse : Chenu C, Adlanmerini M, Boudou F, Chantalat E, Guihot AL, Toutain C, Raymond-Letron I, Vicendo P, Gadeau AP, Henrion D, Arnal JF, Lenfant F. Testosterone Prevents Cutaneous Ischemia and Necrosis in Males Through Complementary Estrogenic and Androgenic Actions. Arterioscler Thromb Vasc Biol. 2017 Mar 30.
• INSERM, Institut des Cordeliers, Paris : Tarjus A, Maase M, Jeggle P, Martinez-Martinez E, Fassot C, Loufrani L, Henrion D, Hansen PBL, Kusche-Vihrog K, Jaisser F. The endothelial αENaC contributes to vascular endothelial function in vivo. PLoS One. 2017;12(9):e0185319.
• Unisersité de Saint-Jacques de Compostelle, Espagne : Valenzuela R, Costa-Besada MA, Iglesias-Gonzalez J, Perez-Costas E, Villar-Cheda B, Garrido-Gil P, Melendez-Ferro M, Soto-Otero R, Lanciego JL, Henrion D, Franco R, Labandeira-Garcia JL. Mitochondrial angiotensin receptors in dopaminergic neurons. Role in cell protection and aging-related vulnerability to neurodegeneration. Cell Death Dis. 2016;7(10):e2427.
• Ecole Vétérinaire (ONIRIS), Nantes : Montaudon E, Dubreil L, Lalanne V, Jagu B, Toumaniantz G, Thorin C, Henrion D, Desfontis JC, Martignat L, Mallem MY. Effects of long-term active immunization with the second extracellular loop of human β1- or β3-adrenoceptors in thoracic aorta and mesenteric arteries in Lewis rats. Vascul Pharmacol. 2016. pii: S1537-1891(16)30159-8.
• CNRS, Sophia-Antipolis, Nice : Retailleau K, Arhatte M, Demolombe S, Peyronnet R, Baudrie V, Jodar M, Bourreau J, Henrion D, Offermanns S, Nakamura F, Feng Y, Patel A, Duprat F, Honoré E. Arterial Myogenic Activation through Smooth Muscle Filamin A. Cell Rep. 2016;14:2050-8.
• INSERM, Unisersité Paris V : Bedarida T, Baron S, Vibert F, Ayer A, Henrion D, Thioulouse E, Marchiol C, Beaudeux JL, Cottart CH, Nivet-Antoine V. Resveratrol Decreases TXNIP mRNA and Protein Nuclear Expressions With an Arterial Function Improvement in Old Mice. J Gerontol A Biol Sci Med Sci. 2015 Jun 3. pii: glv071.
• CRCINA, Nantes-Angers : Marion E, Song OR, Christophe T, Babonneau J, Fenistein D, Eyer J, Letournel F, Henrion D, Clere N, Paille V, Guérineau NC, Saint André JP, Gersbach P, Altmann KH, Stinear TP, Comoglio Y, Sandoz G, Preisser L, Delneste Y, Yeramian E, Marsollier L, Brodin P. Mycobacterial toxin induces analgesia in buruli ulcer by targeting the Angiotensin pathways. Cell. 2014;157:1565-76.
• INSERM, Toulouse: Abot A, Fontaine C, Buscato M, Solinhac R, Flouriot G, Fabre A, Drougard A, Rajan S, Laine M, Milon A, Muller I, Henrion D, Adlanmerini M, Valera MC, Gompel A, Gerard C, Pequeux C, Mestdagt M, Raymond-Letron I, Knauf C, Ferriere F, Valet P, Gourdy P, Katzenellenbogen BS, Katzenellenbogen JA, Lenfant F, Greene GL, Foidart JM, and Arnal JF. The uterine and vascular actions of estetrol delineate a distinctive profile of estrogen receptor alpha modulation, uncoupling nuclear and membrane activation. EMBO Mol Med, 2014.
• INSERM, Toulouse: Adlanmerini M, Solinhac R, Abot A, Fabre A, Raymond-Letron I, Guihot AL, Boudou F, Sautier L, Vessieres E, Kim SH, Liere P, Fontaine C, Krust A, Chambon P, Katzenellenbogen JA, Gourdy P, Shaul PW, Henrion D, Arnal JF, and Lenfant F. Mutation of the palmitoylation site of estrogen receptor alpha in vivo reveals tissue-specific roles for membrane versus nuclear actions. Proc Natl Acad Sci U S A 111: E283-290, 2014.
• Paris V University: Baron S, Bedarida T, Cottart CH, Vibert F, Vessieres E, Ayer A, Henrion D, Hommeril B, Paul JL, Renault G, Saubamea B, Beaudeux JL, Procaccio V, and Nivet-Antoine V. Dual effects of resveratrol on arterial damage induced by insulin resistance in aged mice. J Gerontol A Biol Sci Med Sci 69: 260-269, 2014.
• Paris V University: Bedarida T, Baron S, Vessieres E, Vibert F, Ayer A, Marchiol-Fournigault C, Henrion D, Paul JL, Noble F, Golmard JL, Beaudeux JL, Cottart CH, and Nivet-Antoine V. High-protein-low-carbohydrate diet: deleterious metabolic and cardiovascular effects depend on age. Am J Physiol Heart Circ Physiol 307: H649-657, 2014.
• INSERM, Toulouse: Adlanmerini M, Solinhac R, Abot A, Fabre A, Raymond-Letron I, Guihot AL, Boudou F, Sautier L, Vessieres E, Kim SH, Liere P, Fontaine C, Krust A, Chambon P, Katzenellenbogen JA, Gourdy P, Shaul PW, Henrion D, Arnal JF, and Lenfant F. Mutation of the palmitoylation site of estrogen receptor alpha in vivo reveals tissue-specific roles for membrane versus nuclear actions. Proc Natl Acad Sci U S A 111: E283-E290, 2013
• College de France, INSERM, Paris : Bouleti C, Mathivet T, Coqueran B, Serfaty JM, Lesage M, Berland E, Ardidie-Robouant C, Kauffenstein G, Henrion D, Lapergue B, Mazighi M, Duyckaerts C, Thurston G, Valenzuela DM, Murphy AJ, Yancopoulos GD, Monnot C, Margaill I, and Germain S. Protective effects of angiopoietin-like 4 on cerebrovascular and functional damages in ischaemic stroke. Eur Heart J 34: 3657-3668, 2013
• Charité University, Berlin : Cristofaro B, Shi Y, Faria M, Suchting S, Leroyer AS, Trindade A, Duarte A, Zovein AC, Iruela-Arispe ML, Nih LR, Kubis N, Henrion D, Loufrani L, Todiras M, Schleifenbaum J, Gollasch M, Zhuang ZW, Simons M, Eichmann A, and le Noble F. Dll4-Notch signaling determines the formation of native arterial collateral networks and arterial function in mouse ischemia models. Development 140: 1720-1729, 2013.
• PARCC INSERM, Paris: Bergaya S, Faure S, Baudrie V, Rio M, Escoubet B, Bonnin P, Henrion D, Loirand G, Achard JM, Jeunemaitre X, and Hadchouel J. WNK1 regulates vasoconstriction and blood pressure response to alpha 1-adrenergic stimulation in mice. Hypertension 58: 439-445, 2011.
• INSERM (CRCNA, Nantes-Angers) : Clere N, Corre I, Faure S, Guihot AL, Vessières E, Chalopin M, Morel A, Coqueret O, Hein L, Delneste Y, Paris F, Henrion D. Deficiency or blockade of angiotensin II type 2 receptor delays tumorigenesis by inhibiting malignant cell proliferation and angiogenesis. Int J Cancer, 2010
• PaVé (INRA, Angers): Duge de Bernonville T, Guyot S, Paulin JP, Gaucher M, Loufrani L, Henrion D, Derbre S, Guilet D, Richomme P, Dat JF, Brisset MN. Dihydrochalcones: Implication in resistance to oxidative stress and bioactivities against advanced glycation end-products and vasoconstriction. Phytochemistry. 2010;71:443-52.
• INSERM, Nantes : Guilluy C, Bregeon J, Toumaniantz G, Rolli-Derkinderen M, Retailleau K, Loufrani L, Henrion D, Scalbert E, Bril A, Torres RM, Offermanns S, Pacaud P, Loirand G. The Rho exchange factor Arhgef1 mediates the effects of angiotensin II on vascular tone and blood pressure. Nature Medicine. 2010;16(2):183-90.
• Berlin, « Charité » Hospital : Buschmann I, Pries A, Styp-Rekowska B, Hillmeister P, Shi Y, Duelsner A, Hoefer I, Gatzke N, Wang H, Lehmann K, Henrion D, Loufrani L, Hlushchuk R, Djonov V, le Noble F. Pulsatile shear and Gja5 (Connexin-40) modulate arterial identity and remodeling events during flow driven arteriogenesis. Development, 2010 ;137:2187-96.
• Université de Paris VI- INSERM : Nguyen Dinh Cat A, Griol-Charhbili V, Loufrani L, Labat C, Benjamin L, Farman N, Lacolley P, Henrion D, Jaisser F. The endothelial mineralocorticoid receptor regulates vasoconstrictor tone and blood pressure. FASEB J. 2010;24:2454-63
• Monash University, Melbourne, Australia: Koïtka A, Cao Z, Koh P, Watson AM, Sourris KC, Loufrani L, Soro-Paavonen A, Walther T, Woollard KJ, Jandeleit-Dahm KA, Cooper ME, Allen TJ. Angiotensin II subtype 2 receptor blockade and deficiency attenuate the development of atherosclerosis in an apolipoprotein E-deficient mouse model of diabetes. Diabetologia. 2010;53:584-92
• Université de Lübeck : Lund N, Henrion D, Tiede P, Ziche M, Schunkert H, Ito WD. Vimentin expression influences flow dependent VASP phosphorylation and regulates cell migration and proliferation. Biochem Biophys Res Commun. 2010;395:401-6.
• INSERM, Nancy ; CHU d’Angers: Sennoun N, Baron-Menguy C, Burban M, Lecompte T, Andriantsitohaina R, Henrion D, Mercat A, Asfar P, Levy B, Meziani F. Recombinant human activated protein C improves endotoxemia-induced endothelial dysfunction: A blood free model in isolated mouse arteries. Am J Physiol. 2009, 2009;297:H277-282.
• CNRS – Sofia-Antipolis: Sharif-Naeini R, Folgering JH, Bichet D, Duprat F, Lauritzen I, Arhatte M, Jodar M, Dedman A, Chatelain FC, Schulte U, Retailleau K, Loufrani L, Patel A, Sachs F, Delmas P, Peters DJ, Honoré E. Polycystin-1 and -2 dosage regulates pressure sensing. Cell. 2009 30;139:587-96
• Université de New-York (Valhalla, USA) : Rutkai I, Feher A, Erdei N, Henrion D, Papp Z, Edes I, Koller A, Kaley G, Bagi Z. Activation of prostaglandin E2 EP1 receptor increases arteriolar tone and blood pressure in mice with type 2 diabetes. Cardiovasc Res. 2009;83:148-154.
• Ecole Vétérinaire, Nantes : Delphine Holopherne, Mohamed Yassine Mallem, Eric Belin de Chantemele, Marc Gogny, Daniel Henrion, Jacques Noireaud, Jean-Claude Desfontis. CGP12177-induced hAemodynamic and vascular effects in normotensive and hypertensive rats. Europ. J. Pharmacol. 2008, 591:196-202
• INSERM, Paris : Loufrani L, Retailleau K, Bocquet A, Dumont O, Danker K, Louis H, Lacolley P, Henrion D. Key role of the {alpha}1-{beta}1 integrin in the activation of PI3Kinase-Akt by flow (shear stress) in resistance arteries. Am J Physiol Heart Circ Physiol. 2008;294:H1906-13
• INSERM, Nantes: Guilluy C, Rolli-Derkinderen M, Loufrani L, Bourgé A, Henrion D, Sabourin L, Loirand G, Pacaud P. Ste20-related kinase SLK phosphorylates Ser 188 of RhoA to induce vasodilation in response to Angiotensin II type 2 receptor activation. Circ. Res. 2008;102:1265-74.
• INSERM, Paris : E. Belin de Chantemèle, F. Pinaud, A Bocquet, V. Domenga, L Loufrani, A. Joutel, D. Henrion. Notch3 receptors involvement in the control of vascular mechanotransduction. Arterioscler Thromb Vasc Biol. 2008;28:2216-24.
• CNRS, Nice: Garry A, Fromy B, Blondeau N, Henrion D, Braud F, Gounon P, Guy N, Heurtaux C, Lazdunski M, Saumet JL. Altered acetylcholine and bradykinin and cutaneous pressure-induced vasodilation in mice lacking the TREK-1 potassium channel – The endothelial link. EMBO Rep. 2007 ; 8:354-9.
• INSERM, Paris : Chansel D, Ciroldi M, Vandermeersch S, Jackson LF, Gomez AM, Henrion D, Lee DC, Coffman TM, Richard S, Dussaule JC, Tharaux PL.Heparin binding EGF is necessary for vasospastic response to endothelin. FASEB J. 2006;20:1936-8.
• INSERM, Nancy: Mercier N, Osborne-Pellegrin M, El Hadri K, Kakou A, Labat C, Loufrani L, Henrion D, Challande P, Jalkanen S, Feve B, Lacolley P. Carotid arterial stiffness, elastic fibre network and vasoreactivity in semicarbazide-sensitive amine-oxidase null mouse. Cardiovasc Res. 2006;72:349-57.

Contacts

Postal address

MITOVASC UMR CNRS 6015 INSERM U1083 - Bâtiment IRIS 1 - 4 rue des capucins 49000 Angers tel+ : 02 44 68 82 85

Responsible(s)

guy.lenaers @ univ-angers.fr (guy.lenaers @ univ-angers.fr)

Contacts

Guy Lenaers : 02 44 68 84 87

Catherine Letourmy : 02 44 68 84 85