Toxicologie, Pharmacologie et Signalisation céllulaire - UMR-S 1124
Université Paris Descartes
45 rue des Saints Pères
75270 Paris Cedex 06
Fax : +33 (0) 1 42 86 38 68
Dr. Fatima DJOUADI
INSERM researcher, DR-INSERM
Inborn mitochondrial diseases : pharmacological therapy and metabolic signaling
fatima.djouadi@-Code to remove to avoid SPAM-inserm.fr
+33 1 42 86 22 19, room P470
Our research work aims I) at the identification of molecules, drugs or natural compounds that will correct inborn mitochondrial disorders (defects in fatty acid oxidation, FAO or the respiratory chain, RC) and II) at the identification of new putative therapeutic targets in diverse signaling pathways. Our research is performed mainly on primary cultures of cells obtained from FAO- or RC-deficient patients who have well characterized mutations which allows the pre-clinical evaluation of candidate compounds in a context of personalized medicine.
After several years dedicated to fundamental research on renal physiology in animal models, Fatima Djouadi, Director of Research in the National Institute of Health and Medical Research (INSERM), now is interested in developing new therapeutic strategies for the correction of inborn mitochondrial disorders. The team privileges hypothesis-driven approaches and developes accurate read-outs/endpoints to identify compounds with therapeutic potential for mitochondrial disorders. In particular, we focus on testing drugs, molecules or natural compounds that are known to activate key factors which are involved in the regulation of mitochondrial energy metabolism.
Our experiments are performed preferentially in cultures of patients’ cells (fibroblasts and myoblasts) which allows the analysis of the pharmacological responses as a function of genotype or mutation in panels of different RC or FAO disorders. Over the past years we have demonstrated, for example, that the correction of several genetic mitochondrial disorders can be achieved by pharmacological stimulation of the PPAR/PGC-1α pathway using bezafibrate, a common hypolipidemic drug, or by the use of resveratrol. The concept of target-based pharmacological therapy has been extensively applied to the treatment of common disorders, but has emerged only recently as a promising approach for the treatment of genetic mitochondrial diseases. In line with this, our future projects will continue to explore new hypothesis-driven approaches for the pharmacological therapy of these disorders.
Since 2010: Team leader “Inborn mitochondrial disorders: pharmacological therapy and metabolic signaling”. the National Institute of Health and Medical Research (INSERM) U1124 (Director : Pr. Robert Barouki), Faculty of Fundamental and Medical Sciences, University Paris Descartes School of Medicine, Paris, France.
2006: Principal investigator (CR1) in the National Center for Scientific Research (CNRS) UPR 9078 (Director: Pr. Daniel Ricquier), Necker Hospital, University Paris Descartes School of Medicine, Paris, France.
2000: Principal investigator (CR1) at INSERM U393 (Director: Pr. Arnold Munnich) Necker Hospital, University Paris Descartes School of Medicine, Paris, France.
1996: Visiting Scientist (funded by NATO) in the laboratory of Dr. Daniel P. Kelly’s at the Center of Cardiovascular Research, Washington University School of Medicine, St Louis, Missouri, USA.
1994: Research scientist (CR2) in INSERM U319 (Director: Dr Claudie Merlet-Bénichou), University Pierre and Marie Curie, Paris, France.
1991 : Ph.D. in Developmental Physiology, INSERM U319 (Director : Dr. C. Merlet-Benichou), University Pierre and Marie Curie, Paris, France.
- Resveratrol and Myopathy.
Bastin J, Djouadi F : Nutrients, 2016
- Resveratrol attenuates oxidative stress in mitochondrial Complex I deficiency: Involvement of SIRT3.
Mathieu L, Costa AL, Le Bachelier C, Slama A, Lebre AS, Taylor RW, Bastin J, Djouadi F : Free Radic Biol Med, 2016
- Mitochondrial trifunctional protein deficiency in human cultured fibroblasts: effects of bezafibrate.
Djouadi F, Habarou F, Le Bachelier C, Ferdinandusse S, Schlemmer D, Benoist JF, Boutron A, Andresen BS, Visser G, de Lonlay P, Olpin S, Fukao T, Yamaguchi S, Strauss AW, Wanders RJ, Bastin J : J Inherit Metab Dis, 2015
- Exploring new ways of regulation by resveratrol involving miRNAs, with emphasis on inflammation.
Latruffe N, Lançon A, Frazzi R, Aires V, Delmas D, Michaille JJ, Djouadi F, Bastin J, Cherkaoui-Malki M : Ann N Y Acad Sci, 2015
- Stilbenes and resveratrol metabolites improve mitochondrial fatty acid oxidation defects in human fibroblasts.
Aires V, Delmas D, Le Bachelier C, Latruffe N, Schlemmer D, Benoist JF, Djouadi F, Bastin J : Orphanet J Rare Dis, 2014
- Should the beneficial impact of bezafibrate on fatty acid oxidation disorders be questioned?
Bastin J, Bonnefont JP, Djouadi F, Bresson JL : J Inherit Metab Dis, 2014
- Combination of lipid metabolism alterations and their sensitivity to inflammatory cytokines in human lipin-1-deficient myoblasts.
Michot C, Mamoune A, Vamecq J, Viou MT, Hsieh LS, Testet E, Lainé J, Hubert L, Dessein AF, Fontaine M, Ottolenghi C, Fouillen L, Nadra K, Blanc E, Bastin J, Candon S, Pende M, Munnich A, Smahi A, Djouadi F, Carman GM, Romero N, de Keyzer Y, de Lonlay P : Biochim Biophys Acta, 2013
- Beneficial effects of resveratrol on respiratory chain defects in patients\\’ fibroblasts involve estrogen receptor and estrogen-related receptor alpha signaling.
Lopes Costa A, Le Bachelier C, Mathieu L, Rotig A, Boneh A, De Lonlay P, Tarnopolsky MA, Thorburn DR, Bastin J, Djouadi F : Hum Mol Genet, 2013
- Exposure to resveratrol triggers pharmacological correction of fatty acid utilization in human fatty acid oxidation-deficient fibroblasts.
Bastin J, Lopes-Costa A, Djouadi F : Hum Mol Genet, 2011
- GSH monoethyl ester rescues mitochondrial defects in cystic fibrosis models.
Kelly-Aubert M, Trudel S, Fritsch J, Nguyen-Khoa T, Baudouin-Legros M, Moriceau S, Jeanson L, Djouadi F, Matar C, Conti M, Ollero M, Brouillard F, Edelman A : Hum Mol Genet, 2011
- Species differences in the effects of bezafibrate as a potential treatment of mitochondrial disorders.
Djouadi F, Bastin J : Cell Metab, 2011
- Compared effects of missense mutations in Very-Long-Chain Acyl-CoA Dehydrogenase deficiency: Combined analysis by structural, functional and pharmacological approaches.
Gobin-Limballe S, McAndrew RP, Djouadi F, Kim JJ, Bastin J : Biochim Biophys Acta, 2010
- Bezafibrate for an inborn mitochondrial beta-oxidation defect.
Bonnefont JP, Bastin J, Behin A, Djouadi F : N Engl J Med, 2009
- A potential link between peroxisome proliferator-activated receptor signalling and the pathogenesis of arrhythmogenic right ventricular cardiomyopathy.
Djouadi F, Lecarpentier Y, Hébert JL, Charron P, Bastin J, Coirault C : Cardiovasc Res, 2009
- Bezafibrate for treatment of an inborn mitochondrial ß-oxidation defect.
Bonnefont JP, Bastin J, Behin A, Djouadi F : N Engl J Med, 2009
- Activation of peroxisome proliferator-activated receptor pathway stimulates the mitochondrial respiratory chain and can correct deficiencies in patients\\’ cells lacking its components.
Bastin J, Aubey F, Rötig A, Munnich A, Djouadi F : J Clin Endocrinol Metab, 2008
- Thromboxane synthase mutations in an increased bone density disorder (Ghosal syndrome).
Geneviève D, Proulle V, Isidor B, Bellais S, Serre V, Djouadi F, Picard C, Vignon-Savoye C, Bader-Meunier B, Blanche S, de Vernejoul MC, Legeai-Mallet L, Fischer AM, Le Merrer M, Dreyfus M, Gaussem P, Munnich A, Cormier-Daire V : Nat Genet, 2008
- S6 kinase deletion suppresses muscle growth adaptations to nutrient availability by activating AMP kinase.
Aguilar V, Alliouachene S, Sotiropoulos A, Sobering A, Athea Y, Djouadi F, Miraux S, Thiaudière E, Foretz M, Viollet B, Diolez P, Bastin J, Benit P, Rustin P, Carling D, Sandri M, Ventura-Clapier R, Pende M : Cell Metab, 2007
- Bezafibrate increases very-long-chain acyl-CoA dehydrogenase protein and mRNA expression in deficient fibroblasts and is a potential therapy for fatty acid oxidation disorders.
Djouadi F, Aubey F, Schlemmer D, Ruiter JP, Wanders RJ, Strauss AW, Bastin J : Hum Mol Genet, 2005
- Peroxisome proliferator activated receptor delta (PPARdelta) agonist but not PPARalpha corrects carnitine palmitoyl transferase 2 deficiency in human muscle cells.
Djouadi F, Aubey F, Schlemmer D, Bastin J : J Clin Endocrinol Metab, 2004
- Characterization of fatty acid oxidation in human muscle mitochondria and myoblasts.
Djouadi F, Bonnefont JP, Munnich A, Bastin J : Mol Genet Metab, 2003
- Correction of fatty acid oxidation in carnitine palmitoyl transferase 2-deficient cultured skin fibroblasts by bezafibrate.
Djouadi F, Bonnefont JP, Thuillier L, Droin V, Khadom N, Munnich A, Bastin J : Pediatr Res, 2003
- Mitochondrial and metabolic effects of nucleoside reverse transcriptase inhibitors (NRTIs) in mice receiving one of five single- and three dual-NRTI treatments.
Note R, Maisonneuve C, Lettéron P, Peytavin G, Djouadi F, Igoudjil A, Guimont MC, Biour M, Pessayre D, Fromenty B : Antimicrob Agents Chemother, 2003