Since 2009, Head of Laboratory of Physical and Chemical Biology of Membrane Proteins UMR7099 CNRS University Paris-Diderot, Paris, France.

The laboratory is worldwide known for the atomic structure of the membrane photosynthetic complex b6f and for the development by Jean Luc Popot and co-workers of amphipathic polymers, named Amphipols, that keep membrane proteins in solution [1].

I have introduced two new subjects within the unit:

1. The mitochondrial uncoupling protein UCPs with the long term objective to address the fundamental question of how do they transport protons.

2. The second project is about bio-production of membrane proteins, a subject that I initiated in John Walker laboratory (Cambridge, UK see below). Our long term goal is to design a adapted bacterial host for large scale membrane proliferation and membrane protein production.

Group leader in Daniel Ricquier’s laboratory, Hopital Necker, Paris , France 1997-2009

Ricquier’s lab discovered the mitochondrial uncoupling 2 gene and was the first construct Ucp2 knock out mice [2]. Later on, I have shown that UCP2 modulate reactive oxygen production and promote fatty acid oxidation. Human genetic studies and transgenic mice model pointed out UCP2 as a key gene in inflammation by promoting immune cells activation and proliferation [3-6].

Post-doctoral work: 1993-1997 in John E Walker laboratory (Nobel Prize Winner Chemistry, 1997), Cambridge, Laboratory of Molecular Biology, MRC

Using a simple bacterial genetics approache, I derived T7 RNA polymerase bacterial expression hosts, C41(DE3) and C43(DE3), that are adapted to the large scale production of soluble and membrane proteins ([7], cited over 1000 times Google Scholar). In these mutant hosts, some membrane proteins trigger internal membrane proliferation opening the way to in vivo structural investigation of membrane proteins [8]. A large number of membrane proteins have been crystallized after overproduction in those bacterial strains.

PhD work: laboratory of Dr Daniel Ricquier (CEREMOD, Meudon, France) 1989-93

The Uncoupling Protein (UCP) from brown adipose tissue dissipates the mitochondrial proton electrochemical gradient. In order to understand the molecular basis of heat production by UCP, I have evidenced the first experimental topological model [9], a model confirmed ten years later by the first x-ray structure of the ADP/ATP exchangor [10].

Adapted from [9]. Epitope specific anti-UCP1 antibodies were purified from 7 sheep sera [11]. Antibodies targeting UCP1 epitopes facing the cytosol can be titrated or trapped either by intact mitochondria or submitochondrial particles (see 375-G and 375-B antibodies). In contrast UCP1 antibodies against epitopes facing the matrix side of mitochondria are trapped only with submitochondrial particles. 375-G and 375-J epitopes have opposite topology thus demonstrating the presence of the H1 transmembrane span of UCP1.
Topological model of UCP1 deduced from back titration experiments either on intact mitochondria or submitochondrial particules with epitope specific antibodies. Black boxes represent the position of the epitope, empty boxes the transmembrane span.  For more details see [11-12].

Selected references

   [1] Popot, J.-L. Amphipols, Nanodiscs, and Fluorinated Surfactants: Three Nonconventional Approaches to Studying Membrane Proteins in Aqueous Solutions. Annu. Rev. Biochem. 2010, 79, 737–775
   [2] Arsenijevic, D.; Onuma, H.; Pecqueur, C.; Raimbault, S.; Manning, B. S.; Miroux, B.; Couplan, E.; Alves-Guerra, M. C.; Goubern, M.; Surwit, R.; Bouillaud, F.; Richard, D.; Collins, S.; Ricquier, D. Disruption of the Uncoupling Protein-2 Gene in Mice Reveals a Role in Immunity and Reactive Oxygen Species Production. Nat. Genet. 2000, 26 (4), 435–439
   [3] Alves-Guerra, M.-C.; Rousset, S.; Pecqueur, C.; Mallat, Z.; Blanc, J.; Tedgui, A.; Bouillaud, F.; Cassard-Doulcier, A.-M.; Ricquier, D.; Miroux, B. Bone Marrow Transplantation Reveals the in Vivo Expression of the Mitochondrial Uncoupling Protein 2 in Immune and Nonimmune Cells during Inflammation. J. Biol. Chem. 2003, 278 (43), 42307–42312
   [4] Pecqueur, C.; Alves-Guerra, M. C.; Gelly, C.; Levi-Meyrueis, C.; Couplan, E.; Collins, S.; Ricquier, D.; Bouillaud, F.; Miroux, B. Uncoupling Protein 2, in Vivo Distribution, Induction upon Oxidative Stress, and Evidence for Translational Regulation. J. Biol. Chem. 2001, 276 (12), 8705–8712
  [5] Blanc, J.; Alves-Guerra, M. C.; Esposito, B.; Rousset, S.; Gourdy, P.; Ricquier, D.; Tedgui, A.; Miroux, B.; Mallat, Z. Protective Role of Uncoupling Protein 2 in Atherosclerosis. Circulation 2003, 107 (3), 388–390
   [6] Vogler, S.; Pahnke, J.; Rousset, S.; Ricquier, D.; Moch, H.; Miroux, B.; Ibrahim, S. M. Uncoupling Protein 2 Has Protective Function during Experimental Autoimmune Encephalomyelitis. Am. J. Pathol. 2006, 168 (5), 1570–1575
   [7] Miroux, B.; Walker, J. E. Over-Production of Proteins in Escherichia Coli: Mutant Hosts That Allow Synthesis of Some Membrane Proteins and Globular Proteins at High Levels. J. Mol. Biol. 1996, 260 (3), 289–298
  [8] Arechaga, I.; Miroux, B.; Karrasch, S.; Huijbregts, R.; de Kruijff, B.; Runswick, M. J.; Walker, J. E. Characterisation of New Intracellular Membranes in Escherichia Coli Accompanying Large Scale Over-Production of the b Subunit of F(1)F(o) ATP Synthase. FEBS Lett. 2000, 482 (3), 215–219
   [9] Miroux, B.; Frossard, V.; Raimbault, S.; Ricquier, D.; Bouillaud, F. The Topology of the Brown Adipose Tissue Mitochondrial Uncoupling Protein Determined with Antibodies against Its Antigenic Sites Revealed by a Library of Fusion Proteins. EMBO J 1993, 12 (10), 3739–3745.
   [10]  Pebay-Peyroula, E.; Dahout-Gonzalez, C.; Kahn, R.; Trézéguet, V.; Lauquin, G. J.-M.; Brandolin, G. Structure of Mitochondrial ADP/ATP Carrier in Complex with Carboxyatractyloside. Nature 2003, 426 (6962), 39–44
   [11] Ricquier, D.; Fleury, C.; Larose, M.; Sanchis, D.; Pecqueur, C.; Raimbault, S.; Gelly, C.; Vacher, D.; Cassard-Doulcier, A. M.; Lévi-Meyrueis, C.; Champigny, O.; Miroux, B.; Bouillaud, F. Contributions of Studies on Uncoupling Proteins to Research on Metabolic Diseases. J. Intern. Med. 1999, 245 (6), 637–642
  [12] Miroux, B.; Casteilla, L.; Klaus, S.; Raimbault, S.; Grandin, S.; Clément, J. M.; Ricquier, D.; Bouillaud, F. Antibodies Selected from Whole Antiserum by Fusion Proteins as Tools for the Study of the Topology of Mitochondrial Membrane Proteins. Evidence That the N-Terminal Extremity of the Sixth Alpha-Helix of the Uncoupling Protein Is Facing the Matrix. J Biol Chem 1992, 267 (19), 13603–13609.

Complete Bibliography

Piel, M.S., Masscheleyn, S., Bouillaud, F., Moncoq, K., Miroux, B., 2021. Structural models of mitochondrial uncoupling proteins obtained in DPC micelles are not functionally relevant. FEBS J 288, 3024–3033.
Royes, J., Biou, V., Dautin, N., Tribet, C., Miroux, B., 2020. Inducible intracellular membranes: molecular aspects and emerging applications. Microb. Cell Fact. 19, 176.
Piel, M.S., Masscheleyn, S., Bouillaud, F., Moncoq, K., Miroux, B., 2020. Structural models of mitochondrial uncoupling proteins obtained in DPC micelles are not physiologically relevant for their uncoupling activity. bioRxiv 2020.07.20.195602.
Kanonenberg, K., Royes, J., Kedrov, A., Poschmann, G., Angius, F., Solgadi, A., Spitz, O., Kleinschrodt, D., Stühler, K., Miroux, B., Schmitt, L., 2019. Shaping the lipid composition of bacterial membranes for membrane protein production. Microb. Cell Fact. 18, 131.
Royes, J., Ilioaia, O., Lubart, Q., Angius, F., Dubacheva, G.V., Bally, M., Miroux, B., Tribet, C., 2019. Bacteria-Based Production of Thiol-Clickable, Genetically Encoded Lipid Nanovesicles. Angew. Chem. Int. Ed. Engl. 58, 7395–7399.
Angius, F., Ilioaia, O., Amrani, A., Suisse, A., Rosset, L., Legrand, A., Abou-Hamdan, A., Uzan, M., Zito, F., Miroux, B., 2018. A novel regulation mechanism of the T7 RNA polymerase based expression system improves overproduction and folding of membrane proteins. Sci Rep 8, 8572.
Dilworth, M.V., Piel, M.S., Bettaney, K.E., Ma, P., Luo, J., Sharples, D., Poyner, D.R., Gross, S.R., Moncoq, K., J F Henderson, P., Miroux, B., Bill, R.M., 2018. Microbial expression systems for membrane proteins. Methods 147, 3–39.
Corey, R.A., Pyle, E., Allen, W.J., Watkins, D.W., Casiraghi, M., Miroux, B., Arechaga, I., Politis, A., Collinson, I., 2018. Specific cardiolipin-SecY interactions are required for proton-motive force stimulation of protein secretion. Proc. Natl. Acad. Sci. U.S.A. 115, 7967–7972.
Chipot, C., Dehez, F., Schnell, J.R., Zitzmann, N., Pebay-Peyroula, E., Catoire, L.J., Miroux, B., Kunji, E.R.S., Veglia, G., Cross, T.A., Schanda, P., 2018. Perturbations of Native Membrane Protein Structure in Alkyl Phosphocholine Detergents: A Critical Assessment of NMR and Biophysical Studies. Chem. Rev. 118, 3559–3607.
Hirose, M., Schilf, P., Rohde, S., Gupta, Y., Sancerni, T., Alves-Guerra, M.-C., Sina, C., Jaster, R., Miroux, B., Ibrahim, S.M., 2017. The mitochondrial uncoupling protein 2 gene is causal for the spontaneous polycystic liver diseases in mice. Mitochondrion.
Bouillaud, F., Casteilla, L., Klaus, S., Miroux, B., 2017. Editorial. Biochimie 134, 1–2.
Carranza, G., Angius, F., Ilioaia, O., Solgadi, A., Miroux, B., Arechaga, I., 2017. Cardiolipin plays an essential role in the formation of intracellular membranes in Escherichia coli. Biochim. Biophys. Acta 1859, 1124–1132.
Hirose, M., Schilf, P., Lange, F., Mayer, J., Reichart, G., Maity, P., Jöhren, O., Schwaninger, M., Scharffetter-Kochanek, K., Sina, C., Sadik, C.D., Köhling, R., Miroux, B., Ibrahim, S.M., 2016. Uncoupling protein 2 protects mice from aging. Mitochondrion 30, 42–50.
Angius, F., Ilioaia, O., Uzan, M., Miroux, B., 2016. Membrane Protein Production in Escherichia coli: Protocols and Rules, in: Mus-Veteau, I. (Ed.), Heterologous Expression of Membrane Proteins. Springer New York, New York, NY, pp. 37–52.
Miroux, B., Pebay-Peyroula, E., 2015. Editorial overview: Membranes. Current Opinion in Structural Biology 33, vii–ix.
Hattab, G., Warschawski, D.E., Moncoq, K., Miroux, B., 2015. Escherichia coli as host for membrane protein structure determination: a global analysis. Sci Rep 5, 12097.
Hattab, G., Suisse, A.Y.T., Ilioaia, O., Casiraghi, M., Dezi, M., Warnet, X.L., Warschawski, D.E., Moncoq, K., Zoonens, M., Miroux, B., 2014. Membrane Protein Production in Escherichia coli: Overview and Protocols, in: Mus-Veteau, I. (Ed.), Membrane Proteins Production for Structural Analysis. Springer New York, pp. 87–106.
Zoonens, M., Comer, J., Masscheleyn, S., Pebay-Peyroula, E., Chipot, C., Miroux, B., Dehez, F., 2013. Dangerous liaisons between detergents and membrane proteins. The case of mitochondrial uncoupling protein 2. J. Am. Chem. Soc. 135, 15174–15182.
Blesneac, I., Ravaud, S., Machillot, P., Zoonens, M., Masscheylen, S., Miroux, B., Vivaudou, M., Pebay-Peyroula, E., 2012. Assaying the proton transport and regulation of UCP1 using solid supported membranes. Eur. Biophys. J. 41, 675–679.
Scheffler, K., Krohn, M., Dunkelmann, T., Stenzel, J., Miroux, B., Ibrahim, S., von Bohlen Und Halbach, O., Heinze, H.-J., Walker, L.C., Gsponer, J.A., Pahnke, J., 2012. Mitochondrial DNA polymorphisms specifically modify cerebral β-amyloid proteostasis. Acta Neuropathol. 124, 199–208.
Blesneac, I., Ravaud, S., Juillan-Binard, C., Barret, L.-A., Zoonens, M., Polidori, A., Miroux, B., Pucci, B., Pebay-Peyroula, E., 2012. Production of UCP1 a membrane protein from the inner mitochondrial membrane using the cell free expression system in the presence of a fluorinated surfactant. Biochim. Biophys. Acta 1818, 798–805.
Gimsa, U., Kanitz, E., Otten, W., Aheng, C., Tuchscherer, M., Ricquier, D., Miroux, B., Ibrahim, S.M., 2011. Alterations in anxiety-like behavior following knockout of the uncoupling protein 2 (ucp2) gene in mice. Life Sci. 89, 677–684.
Aheng, C., Ly, N., Kelly, M., Ibrahim, S., Ricquier, D., Alves-Guerra, M.-C., Miroux, B., 2011. Deletion of UCP2 in iNOS deficient mice reduces the severity of the disease during experimental autoimmune encephalomyelitis. PLoS ONE 6, e22841.
Zoonens, M., Miroux, B., 2010. Expression of membrane proteins at the Escherichia coli membrane for structural studies. Methods Mol. Biol. 601, 49–66.
Pecqueur, C., Bui, T., Gelly, C., Hauchard, J., Barbot, C., Bouillaud, F., Ricquier, D., Miroux, B., Thompson, C.B., 2007. Uncoupling protein-2 controls proliferation by promoting fatty acid oxidation and limiting glycolysis-derived pyruvate utilization. The FASEB Journal 22, 9–18.
Yakubu, D.P., Mostyn, A., Wilson, V., Pearce, S., Alves-Guerra, M.C., Pecqueur, C., Miroux, B., Budge, H., Stephenson, T., Symonds, M.E., 2007. Different effects of maternal parity, cold exposure and nutrient restriction in late pregnancy on the abundance of mitochondrial proteins in the kidney, liver and lung of postnatal sheep. Reproduction 133, 1241–1252.
Bensalem, N., Masscheleyn, S., Mozo, J., Vallée, B., Brouillard, F., Trudel, S., Ricquier, D., Edelman, A., Guerrera, I.C., Miroux, B., 2007. High sensitivity identification of membrane proteins by MALDI TOF-MASS spectrometry using polystyrene beads. J. Proteome Res. 6, 1595–1602.
Chevillotte, E., Giralt, M., Miroux, B., Ricquier, D., Villarroya, F., 2007. Uncoupling protein-2 controls adiponectin gene expression in adipose tissue through the modulation of reactive oxygen species production. Diabetes 56, 1042–1050.
Vogler, S., Pahnke, J., Rousset, S., Ricquier, D., Moch, H., Miroux, B., Ibrahim, S.M., 2006. Uncoupling protein 2 has protective function during experimental autoimmune encephalomyelitis. Am. J. Pathol. 168, 1570–1575.
Mozo, J., Ferry, G., Masscheleyn, S., Miroux, B., Boutin, J.A., Bouillaud, F., 2006. Assessment of a high-throughput screening methodology for the measurement of purified UCP1 uncoupling activity. Anal. Biochem. 351, 201–206.
Criscuolo, F., Gonzalez-Barroso, M. del M., Bouillaud, F., Ricquier, D., Miroux, B., Sorci, G., 2005. Mitochondrial uncoupling proteins: new perspectives for evolutionary ecologists. Am. Nat. 166, 686–699.
Gnanalingham, M.G., Mostyn, A., Webb, R., Keisler, D.H., Raver, N., Alves-Guerra, M.C., Pecqueur, C., Miroux, B., Symonds, M.E., Stephenson, T., 2005. Differential effects of leptin administration on the abundance of UCP2 and glucocorticoid action during neonatal development. Am. J. Physiol. Endocrinol. Metab. 289, E1093-1100.
Gnanalingham, M.G., Mostyn, A., Wang, J., Webb, R., Keisler, D.H., Raver, N., Alves-Guerra, M.C., Pecqueur, C., Miroux, B., Stephenson, T., Symonds, M.E., 2005. Tissue-specific effects of leptin administration on the abundance of mitochondrial proteins during neonatal development. J. Endocrinol. 187, 81–88.
Haguenauer, A., Raimbault, S., Masscheleyn, S., Gonzalez-Barroso, M. del M., Criscuolo, F., Plamondon, J., Miroux, B., Ricquier, D., Richard, D., Bouillaud, F., Pecqueur, C., 2005. A new renal mitochondrial carrier, KMCP1, is up-regulated during tubular cell regeneration and induction of antioxidant enzymes. J. Biol. Chem. 280, 22036–22043.
Mostyn, A., Litten, J.C., Perkins, K.S., Alves-Guerra, M.C., Pecqueur, C., Miroux, B., Symonds, M.E., Clarke, L., 2004. Influence of genotype on the differential ontogeny of uncoupling protein 2 and 3 in subcutaneous adipose tissue and muscle in neonatal pigs. J. Endocrinol. 183, 121–131.
Rousset, S., Alves-Guerra, M.-C., Mozo, J., Miroux, B., Cassard-Doulcier, A.-M., Bouillaud, F., Ricquier, D., 2004. The biology of mitochondrial uncoupling proteins. Diabetes 53 Suppl 1, S130-135.
Rousset, S., Alves-Guerra, M.-C., Ouadghiri-Bencherif, S., Kozak, L.P., Miroux, B., Richard, D., Bouillaud, F., Ricquier, D., Cassard-Doulcier, A.-M., 2003. Uncoupling protein 2, but not uncoupling protein 1, is expressed in the female mouse reproductive tract. J. Biol. Chem. 278, 45843–45847.
Alves-Guerra, M.-C., Rousset, S., Pecqueur, C., Mallat, Z., Blanc, J., Tedgui, A., Bouillaud, F., Cassard-Doulcier, A.-M., Ricquier, D., Miroux, B., 2003. Bone marrow transplantation reveals the in vivo expression of the mitochondrial uncoupling protein 2 in immune and nonimmune cells during inflammation. J. Biol. Chem. 278, 42307–42312.
Mostyn, A., Wilson, V., Dandrea, J., Yakubu, D.P., Budge, H., Alves-Guerra, M.C., Pecqueur, C., Miroux, B., Symonds, M.E., Stephenson, T., 2003. Ontogeny and nutritional manipulation of mitochondrial protein abundance in adipose tissue and the lungs of postnatal sheep. Br. J. Nutr. 90, 323–328.
Winzell, M.S., Svensson, H., Enerbäck, S., Ravnskjaer, K., Mandrup, S., Esser, V., Arner, P., Alves-Guerra, M.-C., Miroux, B., Sundler, F., Ahrén, B., Holm, C., 2003. Pancreatic beta-cell lipotoxicity induced by overexpression of hormone-sensitive lipase. Diabetes 52, 2057–2065.
Arechaga, I., Miroux, B., Runswick, M.J., Walker, J.E., 2003. Over-expression of Escherichia coli F1F(o)-ATPase subunit a is inhibited by instability of the uncB gene transcript. FEBS Lett. 547, 97–100.
Pearce, S., Mostyn, A., Alves-Guerra, M.C., Pecqueur, C., Miroux, B., Webb, R., Stephenson, T., Symond, M.E., 2003. Prolactin, prolactin receptor and uncoupling proteins during fetal and neonatal development. Proc Nutr Soc 62, 421–427.
Blanc, J., Alves-Guerra, M.C., Esposito, B., Rousset, S., Gourdy, P., Ricquier, D., Tedgui, A., Miroux, B., Mallat, Z., 2003. Protective role of uncoupling protein 2 in atherosclerosis. Circulation 107, 388–390.
Shaw, A.Z., Miroux, B., 2003. A general approach for heterologous membrane protein expression in Escherichia coli: the uncoupling protein, UCP1, as an example. Methods Mol. Biol. 228, 23–35.
Hourton-Cabassa, C., Mesneau, A., Miroux, B., Roussaux, J., Ricquier, D., Zachowski, A., Moreau, F., 2002. Alteration of plant mitochondrial proton conductance by free fatty acids. Uncoupling protein involvement. J. Biol. Chem. 277, 41533–41538.
Steinfels, E., Orelle, C., Dalmas, O., Penin, F., Miroux, B., Di Pietro, A., Jault, J.-M., 2002. Highly efficient over-production in E. coli of YvcC, a multidrug-like ATP-binding cassette transporter from Bacillus subtilis. Biochim. Biophys. Acta 1565, 1–5.
Pecqueur, C., Alves-Guerra, M.C., Gelly, C., Levi-Meyrueis, C., Couplan, E., Collins, S., Ricquier, D., Bouillaud, F., Miroux, B., 2001. Uncoupling protein 2, in vivo distribution, induction upon oxidative stress, and evidence for translational regulation. J. Biol. Chem. 276, 8705–8712.
Arsenijevic, D., Onuma, H., Pecqueur, C., Raimbault, S., Manning, B.S., Miroux, B., Couplan, E., Alves-Guerra, M.C., Goubern, M., Surwit, R., Bouillaud, F., Richard, D., Collins, S., Ricquier, D., 2000. Disruption of the uncoupling protein-2 gene in mice reveals a role in immunity and reactive oxygen species production. Nat. Genet. 26, 435–439.
Arechaga, I., Miroux, B., Karrasch, S., Huijbregts, R., de Kruijff, B., Runswick, M.J., Walker, J.E., 2000. Characterisation of new intracellular membranes in Escherichia coli accompanying large scale over-production of the b subunit of F(1)F(o) ATP synthase. FEBS Lett. 482, 215–219.
Ricquier, D., Miroux, B., Larose, M., Cassard-Doulcier, A.M., Bouillaud, F., 2000. Endocrine regulation of uncoupling proteins and energy expenditure. Int. J. Obes. Relat. Metab. Disord. 24 Suppl 2, S86-88.