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Mitochondrial and Cardiovascular Physiopathology | UMR Inserm U1083 - CNRS 6015
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Separated by coma

Clinical and pre-clinical metabolomics and lipidomics in mitochondrial disorders and dysfunctions

Pascal reynier, University Professor - Hospital Practitioner

(pareynier @ chu-angers.fr)

 

pareynier @ chu-angers.fr

 

Keywords : Mitochondria, Metabolomics, Lipidomics

 

 State of the art and objectives

At the crossroad between biochemistry and mathematics, metabolomics is a powerful tool for biomarkers and drug discovery in clinical and experimental studies. We have developed three metabolomic pipelines allowing the analysis of more than 1000 polar metabolites and lipids to explore the mitochondrial dysfunctions in diseases and experimental models. Multivariate statistical modelling and machine learning approaches are used to identify the biological fingerprints of these diseases and experimental models. This approach was found very powerful since discriminant models were obtained in most of the conditions tested, and several of these studies have revealed new therapeutic avenues.

Main results from the last 5 years

We have contributed to characterize the metabolomic and lipidomic signatures in the following clinical studies:

  • Primary Open Angle Glaucoma (plasma and aqueous humor)
  • Exfoliation syndrome (plasma)
  • Leber Hereditary Optic Neuropathy (fibroblasts)
  • OPA1-related Dominant Optic Atrophy (plasma, fibroblasts)
  • Amyotrophic Lateral Sclerosis (cerebrospinal fluid, fibroblasts)
  • Cardiac Remote Ischemic Preconditioning (serum)
  • Ovary insufficiency (follicular fluid)
  • Hypothermia fatalities (serum, urines, vitreous humor)

We have contributed to characterize the metabolomic and lipidomic signatures in the following pre-clinical studies:

  • Cardiac Remote Ischemic Preconditioning (rat, serum)
  • OPA1-related Dominant Optic Atrophy (Opa1+/- mouse model, Opa1-/- mouse embryonic fibroblasts)
  • Retinal preconditioning light stress (rat, retina)
  • Obesity-induced metabolic disturbance in the retina (rat)
  • Metabolomics of combined mitochondrial + endoplasmic reticulum fraction (human fibroblasts)

Mitolab metabolomics team

  • Dr Juan Manuel Chao de la Barca (MD, PhD)
  • Dr Judith Kouassy Nzoughet (PhD)
  • Dr Cinzia Bocca (PhD)
  • Dr Gilles Simard (MD, PhD)
  • Pr Delphine Mirebeau-Prunier (MD, PhD)

Main Collaborations:

  • Mitochondrial diseases and inherited optic neuropathies: Dr Guy Lenaers, Pr Vincent Procaccio, Pr Dominique Bonneau, Dr Christophe Verny, Dr Patrizia Amati-Bonneau, Dr Gilles Simard, Dr Julien Cassereau, Dr Magalie Barth, Dr Naïg Gueguen, Dr Valérie Desquiret-Dumas, Dr Céline Bris, Dr David Goudenège, Dr Marc Ferré, Dr Philippe Codron
  • Mitochondrial dysfunctions: Dr Arnaud Chevrollier, Dr Olivier Baris, Dr Selam Kane, Dr Salim Khiati, Dr Jamal Wakim,
  • Ophtalmo-metabolomics: Pr Dan Milea, Dr Philippe Gohier, Dr Stéphanie Leruez
  • Mitochondria, metabolomics and fertility: Dr Pascale May-Panloup, Dr Pierre-Emmanuel Bouet
  • LOVD databases on inherited optic neuropathies: Dr Marc Ferré
  • Cardiac remote ischemic preconditioning: Pr Fabrice Prunier, Pr Delphine Mirebeau-Prunier
  • Forensic medicine: Dr Guillaume Rousseau, Pr Clotilde Rougé-Maillart
  • Sjögren syndrome: Dr Geoffrey Urbanski, Pr Christian Lavigne
  • Amyotrophic lateral sclerosis: Pr Christian Andres, Pr Hélène Blasco, Dr Charlotte Veyrat-Durebex
  • Placenta insufficiency: Pr Geraldine Gascoin, M. Floris Chabrun
  • Sickle cell disease: Dr Casimir Dembélé, Pr Aldiouma Guindo
  • Peripheral arteriopathies: Pr Pierre Abraham
  • RET oncogene: Pr Mirebeau-Prunier, Dr Charlotte Veyrat-Durebex
  • Fluxomics in mitochondrial dysfonctions: Pr Guillaume Tcherkez
  • Hypertension: Dr Yaya Goita

 

Main publications and patents from the 5 last years (2014-2018)

  • Bonneau D, Colin E, Oca F, Ferré M, Chevrollier A, Guéguen N, Desquiret-Dumas V, N'Guyen S, Barth M, Zanlonghi X, Rio M, Desguerre I, Barnerias C, Momtchilova M, Rodriguez D, Slama A, Lenaers G, Procaccio V, Amati-Bonneau P, Reynier P. Early-onset Behr syndrome due to compound heterozygous mutations in OPA1. Brain 2014;137:e301.
  •  Leruez S, Amati-Bonneau P, Verny C, Reynier P, Procaccio V, Bonneau D, Milea D. Mitochondrial dysfunction affecting visual pathways. Revue Neurologique (Paris) 2014;170:344-54.
  •  Procaccio V, Bris C, Chao de la Barca JM, Oca F, Chevrollier A, Amati-Bonneau P, Bonneau D, Reynier P. Perspectives of drug-based neuroprotection targeting mitochondria. Revue Neurologique (Paris) 2014;170:390-400.)
  •  Homedan C, Laafi J, Schmitt C, Gueguen N, Lefebvre T, Karim Z, Desquiret-Dumas V, Wetterwald C, Deybach JC, Gouya L, Puy H, Reynier P, Malthièry Y. Acute intermittent porphyria causes hepatic mitochondrial energetic failure in a mouse model. International Journal Of Biochemistry and Cell Biology 2014;51:93-101.
  •  Ferré M, Amati-Bonneau P, Morinière C, Ferré-L'Hôtellier V, Lemerle S, Przyrowski D, Procaccio V, Descamps P, Reynier P, May-Panloup P. Are zona pellucida genes involved in recurrent oocyte lysis observed during in vitro fertilization? Journal of Assisted reproduction and Genetics 2014;31:221-7.
  •  May-Panloup P, Desquiret V, Morinière C, Ferré-L'Hôtellier V, Lemerle S, Boucret L, Lehais S, Chao de la Barca JM, Descamps P, Procaccio V, Reynier P. Mitochondrial macro-haplogroup JT may play a protective role in ovarian ageing. Mitochondrion 2014;18:1-6.
  •  Laafi J, Homedan C, Jacques C, Gueguen N, Schmitt C, Puy H, Reynier P, Carmen Martinez M, Malthièry Y. Pro-oxidant effect of ALA is implicated in mitochondrial dysfunction of HepG2 cells. Biochimie 2014;106:157-66.
  •  Cottin L, Rouvet C, Homedan C, Conté M, Mortaza S, Rousselet MC, Corby A, Le Guyader M, Zandecki M, Reynier P. [Multiorgan failure after sickle cell vaso occlusive attack: integrated clinical and biological emergency]. Annales de Biologie Clinique (Paris) 2014;72:602-6.
  •  Dufour-Rainfray D, Moal V, Cloix L, Mathieu E, Gauchez AS, Brossaud J, Corcuff JB, Fraissinet F, Collet C, Boux de Casson F, Guilloteau D, Emond P, Reynier P. [Mass spectrometry for steroid assays]. Annales de Biologie Clinique (Paris) 2015;73:70-8.
  •  Chao De La Barca JM, Mirebeau-Prunier D, Moal V, Reynier P, Garnotel R, Simard G. [Metabolome and mass spectrometry: new biomedical analysis perspectives]. Annales de Biologie Clinique (Paris) 2015;73:126-30.
  •  Jourdain AA, Koppen M, Rodley CD, Maundrell K, Gueguen N, Reynier P, Guaras AM, Enriquez JA, Anderson P, Simarro M, Martinou JC. A Mitochondria-Specific Isoform of FASTK Is Present In Mitochondrial RNA Granules and Regulates Gene Expression and Function. Cell Report 2015;10:1110-21.
  •  Ferré M, Caignard A, Milea D, Leruez S, Cassereau J, Chevrollier A, Amati-Bonneau P, Verny C, Bonneau D, Procaccio V, Reynier P. Improved locus-specific database for OPA1 mutations allows inclusion of advanced clinical data. Human Mutation 2015;36:20-5.
  •  Li Z, Allingham RR, Nakano M, Jia L, Chen Y, Ikeda Y, Mani B, Chen LJ, Kee C, Garway-Heath DF, Sripriya S, Fuse N, Abu-Amero KK, Huang C, Namburi P, Burdon K, Perera SA, Gharahkhani P, Lin Y, Ueno M, Ozaki M, Mizoguchi T, Krishnadas SR, Osman EA, Lee MC, Chan AS, Tajudin LS, Do T, Goncalves A, Reynier P, Zhang H, Bourne R, Goh D, Broadway D, Husain R, Negi AK, Su DH, Ho CL, Blanco AA, Leung CK, Wong TT, Yakub A, Liu Y, Nongpiur ME, Han JC, Hon do N, Shantha B, Zhao B, Sang J, Zhang N, Sato R, Yoshii K, Panda-Jonas S, Ashley Koch AE, Herndon LW, Moroi SE, Challa P, Foo JN, Bei JX, Zeng YX, Simmons CP, Bich Chau TN, Sharmila PF, Chew M, Lim B, Tam PO, Chua E, Ng XY, Yong VH, Chong YF, Meah WY, Vijayan S, Seongsoo S, Xu W, Teo YY, Cooke Bailey JN, Kang JH, Haines JL, Cheng CY, Saw SM, Tai ES; ICAARE-Glaucoma Consortium; NEIGHBORHOOD Consortium, Richards JE, Ritch R, Gaasterland DE, Pasquale LR, Liu J, Jonas JB, Milea D, George R, Al-Obeidan SA, Mori K, Macgregor S, Hewitt AW, Girkin CA, Zhang M, Sundaresan P, Vijaya L, Mackey DA, Wong TY, Craig JE, Sun X, Kinoshita S, Wiggs JL, Khor CC, Yang Z, Pang CP, Wang N, Hauser MA, Tashiro K, Aung T, Vithana EN. A common variant near TGFBR3 is associated with primary open angle glaucoma. Human Molecular Genetics 2015;24:3880-92.
  •  Boucret L, Chao de la Barca JM, Morinière C, Desquiret V, Ferré-L'Hôtellier V, Descamps P, Marcaillou C, Reynier P, Procaccio V, May-Panloup P. Relationship between diminished ovarian reserve and mitochondrial biogenesis in cumulus cells. Human Reproduction 2015;30:1653-64.
  •  Leman G, Gueguen N, Desquiret-Dumas V, Kane MS, Wettervald C, Chupin S, Chevrollier A, Lebre AS, Bonnefont JP, Barth M, Amati-Bonneau P, Verny C, Henrion D, Bonneau D, Reynier P, Procaccio V. Assembly defects induce oxidative stress in inherited mitochondrial complex I deficiency. International Journal Of Biochemistry and Cell Biology 2015;65:91-103.
  •  Lasserre JP, Dautant A, Aiyar RS, Kucharczyk R, Glatigny A, Tribouillard-Tanvier D, Rytka J, Blondel M, Skoczen N, Reynier P, Pitayu L, Rötig A, Delahodde A, Steinmetz LM, Dujardin G, Procaccio V, di Rago JP. Yeast as a system for modeling mitochondrial disease mechanisms and discovering therapies. Disease Models and Mechanisms 2015;8:509-26.
  •  Homedan C, Schmitt C, Laafi J, Gueguen N, Desquiret-Dumas V, Lenglet H, Karim Z, Gouya L, Deybach JC, Simard G, Puy H, Malthièry Y, Reynier P. Mitochondrial energetic defects in muscle and brain of a Hmbs-/- mouse model of acute intermittent porphyria. Human Molecular Genetics 2015;24:5015-23.
  •  Six E, Lagresle-Peyrou C, Susini S, De Chappedelaine C, Sigrist N, Sadek H, Chouteau M, Cagnard N, Fontenay M, Hermine O, Chomienne C, Reynier P, Fischer A, André-Schmutz I, Gueguen N, Cavazzana M. AK2 deficiency compromises the mitochondrial energy metabolism required for differentiation of human neutrophil and lymphoid lineages. Cell Death Discovery 2015;6:e1856.
  •  Chao de la Barca JM, Prunier-Mirebeau D, Amati-Bonneau P, Ferré M, Sarzi E, Bris C, Leruez S, Chevrollier A, Desquiret-Dumas V, Gueguen N, Verny C, Hamel C, Miléa D, Procaccio V, Bonneau D, Lenaers G, Reynier P. OPA1-related disorders: Diversity of clinical expression, modes of inheritance and pathophysiology. Neurobiology of Diseases 2016;90:20-6.
  •  Girard JM, Debailleul PA, Chaillou E, Benlian P, Larcher F, Simard G, Reynier P, Homedan C. Type I hyperlipidaemia caused by lipoprotein lipase deficiency in a nurseling: the role of the clinical laboratory in processing biological samples and contributing to the diagnosis and therapeutic follow-up of patients. Annales de Biologie Clinique (Paris) 2015 ;73:581-6.
  •  Angebault C, Guichet PO, Talmat-Amar Y, Charif M, Gerber S, Fares-Taie L, Gueguen N, Halloy F, Moore D, Amati-Bonneau P, Manes G, Hebrard M, Bocquet B, Quiles M, Piro-Mégy C, Teigell M, Delettre C, Rossel M, Meunier I, Preising M, Lorenz B, Carelli V, Chinnery PF, Yu-Wai-Man P, Kaplan J, Roubertie A, Barakat A, Bonneau D, Reynier P, Rozet JM, Bomont P, Hamel CP, Lenaers G. Recessive Mutations in RTN4IP1 Cause Isolated and Syndromic Optic Neuropathies. American Journal of Human Genetics 2015;97:754-60.
  •  Gueguen N, Desquiret-Dumas V, Leman G, Chupin S, Baron S, Nivet-Antoine V, Vessières E, Ayer A, Henrion D, Lenaers G, Reynier P, Procaccio V. Resveratrol Directly Binds to Mitochondrial Complex I and Increases Oxidative Stress in Brain Mitochondria of Aged Mice. PLoS One 2015;10:e0144290.
  •  Sarzi E, Seveno M, Angebault C, Milea D, Rönnbäck C, Quilès M, Adrian M, Grenier J, Caignard A, Lacroux A, Lavergne C, Reynier P, Larsen M, Hamel CP, Lenaers G, Müller A. Increased steroidogenesis promotes early-onset and severe vision loss in females with OPA1 dominant optic atrophy. Human Molecular Genetics 2016;25:2539-2551.
  •  Buret L, Rebillard G, Brun E, Angebault C, Pequignot M, Lenoir M, Do-Cruzeiro M, Tournier E, Cornille K, Saleur A, Gueguen N, Reynier P, Amati-Bonneau P, Barakat A, Blanchet C, Chinnery P, Yu-Wai-Man P, Kaplan J, Roux AF, Van Camp G, Wissinger B, Boespflug-Tanguy O, Giraudet F, Puel JL, Lenaers G, Hamel C, Delprat B, Delettre C. Loss of function of Ywhah in mice induces deafness and cochlear outer hair cells' degeneration. Cell Death Discovery 2016;2:16017.
  •  Colin E, Daniel J, Ziegler A, Wakim J, Scrivo A, Haack TB, Khiati S, Denommé AS, Amati-Bonneau P, Charif M, Procaccio V, Reynier P, Aleck KA, Botto LD, Herper CL, Kaiser CS, Nabbout R, N'Guyen S, Mora-Lorca JA, Assmann B, Christ S, Meitinger T, Strom TM, Prokisch H; FREX Consortium., Miranda-Vizuete A, Hoffmann GF, Lenaers G, Bomont P, Liebau E, Bonneau D. Biallelic Variants in UBA5 Reveal that Disruption of the UFM1 Cascade Can Result in Early-Onset Encephalopathy. American Journal of Human Genetics 2016;99:695-703.
  •  Millet AM, Bertholet AM, Daloyau M, Reynier P, Galinier A, Devin A, Wissinguer B, Belenguer P, Davezac N. Loss of functional OPA1 unbalances redox state: implications in dominant optic atrophy pathogenesis. Annals of Clinical an Translational Neurology 2016;3:408-21.
  •  May-Panloup P, Boucret L, Chao de la Barca JM, Desquiret-Dumas V, Ferré-L'Hotellier V, Morinière C, Descamps P, Procaccio V, Reynier P. Ovarian ageing: the role of mitochondria in oocytes and follicles. Human Reproduction Update 2016;22:725-743.
  •  Signolet I, Chenouard R, Oca F, Barth M, Reynier P, Denis MC, Simard G. Recurrent Isolated Neonatal Hemolytic Anemia: Think About Glutathione Synthetase Deficiency. Pediatrics 2016;138(3).
  •  Chao de la Barca JM, Simard G, Amati-Bonneau P, Safiedeen Z, Prunier-Mirebeau D, Chupin S, Gadras C, Tessier L, Gueguen N, Chevrollier A, Desquiret-Dumas V, Ferré M, Bris C, Kouassi Nzoughet J, Bocca C, Leruez S, Verny C, Miléa D, Bonneau D, Lenaers G, Martinez MC, Procaccio V, Reynier P. The metabolomic signature of Leber's hereditary optic neuropathy reveals endoplasmic reticulum stress. Brain  2016;139:2864-2876.
  •  Chao de la Barca JM, Bakhta O, Kalakech H, Simard G, Tamareille S, Catros V, Callebert J, Gadras C, Tessier L, Reynier P, Prunier F, Mirebeau-Prunier D. Metabolic Signature of Remote Ischemic Preconditioning Involving a Cocktail of Amino Acids and Biogenic Amines. Journal Of American Heart Association 2016;5.
  •  Codron P, Chevrollier A, Kane MS, Echaniz-Laguna A, Latour P, Reynier P, Bonneau D, Verny C, Procaccio V, Lenaers G, Cassereau J. Increased mitochondrial fusion in a autosomal recessive CMT2A family with mitochondrial GTPase mitofusin 2 mutations. J Peripheral Nerve System 2016;21:365-369.
  • Le Page S, Niro M, Fauconnier J, Cellier L, Tamareille S, Gharib A, Chevrollier A, Loufrani L, Grenier C, Kamel R, Sarzi E, Lacampagne A, Ovize M, Henrion D, Reynier P, Lenaers G, Mirebeau-Prunier D, Prunier F. Increase in Cardiac Ischemia-Reperfusion Injuries in Opa1+/- Mouse Model. PLoS One 2016;11:e0164066.
  •  Frey S, Geffroy G, Desquiret-Dumas V, Gueguen N, Bris C, Belal S, Amati-Bonneau P, Chevrollier A, Barth M, Henrion D, Lenaers G, Bonneau D, Reynier P, Procaccio V. The addition of ketone bodies alleviates mitochondrial dysfunction by restoring complex I assembly in a MELAS cellular model. Biochimica Biophysica Acta 2017;1863:284-291.
  •  Girard JM, Drevin G, Brasme JF, Pissard S, Reynier P, Simard G, Denis MC. Clinical and biological specificity of beta-thalassemia intermedia: a case report. Annales de Biologie Clinique (Paris) 2016;74:688-692.
  •  Loo JL, Singhal S, Rukmini AV, Tow S, Amati-Bonneau P, Procaccio V, Bonneau D, Gooley JJ, Reynier P, Ferré M, Milea D. Multiethnic involvement in autosomal-dominant optic atrophy in Singapore. Eye (Lond) 2017;31:475-480].
  • Kouassi Nzoughet J, Bocca C, Simard G, Prunier-Mirebeau D, Chao de la Barca JM, Bonneau D, Procaccio V, Prunier F, Lenaers G, Reynier P. A Nontargeted UHPLC-HRMS Metabolomics Pipeline for Metabolite Identification: Application to Cardiac Remote Ischemic Preconditioning. Analytical Chemistry 2017;89:2138-2146.
  •  Desquiret-Dumas V, Clément A, Seegers V, Boucret L, Ferré-L'Hotellier V, Bouet PE, Descamps P, Procaccio V, Reynier P, May-Panloup P. The mitochondrial DNA content of cumulus granulosa cells is linked to embryo quality. Human Reproduction 2017;32:607-614.
  •  Chao de la Barca JM, Simard G, Sarzi E, Chaumette T, Rousseau G, Chupin S, Gadras C, Tessier L, Ferré M, Chevrollier A, Desquiret-Dumas V, Gueguen N, Leruez S, Verny C, Miléa D, Bonneau D, Amati-Bonneau P, Procaccio V, Hamel C, Lenaers G, Reynier P, Prunier-Mirebeau D. Targeted Metabolomics Reveals Early Dominant Optic Atrophy Signature in Optic Nerves of Opa1delTTAG/+ Mice. Investigative Ophthalmology and Visual Science 2017;58:812-820.
  •  Chao de la Barca J, Ting Huan N, Jiao H, Tessier L, Gadras C, Simard G, Natoli R, Tcherkez G, Reynier P, Valter K. Retinal metabolic events in preconditioning light stress as revealed by wide-spectrum targeted metabolomics. Metabolomics 2017;13:22.
  • Boueilh T, Bassi C, Rouleau S, Le Crugel S, Moal V, Boux de Casson F, Coutant R, Mirebeau-Prunier D, Reynier P, Homedan C. Pituitary stalk interruption syndrome: a rare and severe cause of pituitary deficiency Laboratory diagnosis of a newborn case. Annales de Biologie clinique (Paris). 2017;75:215-221.
  • Prunier F, Reynier P, Mirebeau-Prunier D. Letter in response to remote ischaemic conditioning provides humoral cross-species cardioprotection through glycine receptor activation. Cardiovascular Research 2017;113:562.
  •  Kane MS, Alban J, Desquiret-Dumas V, Gueguen N, Ishak L, Ferre M, Amati-Bonneau P, Procaccio V, Bonneau D, Lenaers G, Reynier P, Chevrollier A. Autophagy controls the pathogenicity of OPA1 mutations in dominant optic atrophy. Journal of Cellular and Molecular Medicine 2017;21:2284-2297.
  • Wakim J, Goudenege D, Perrot R, Gueguen N, Desquiret-Dumas V, de la Barca JMC, Rosa ID, Manero F, Le Mao M, Chupin S, Chevrollier A, Procaccio V, Bonneau D, Logan DC, Reynier P, Lenaers G, Khiati S. CLUH couples mitochondrial distribution to the energetic and metabolic status. Journal of Cell Science 2017;130:1940-1951.
  •  Verny C, Bachoud-Lévi AC, Durr A, Goizet C, Azulay JP, Simonin C, Tranchant C, Calvas F, Krystkowiak P, Charles P, Youssov K, Scherer C, Prundean A, Olivier A, Reynier P, Saudou F, Maison P, Allain P, von Studnitz E, Bonneau D; CYST-HD Study Group. A randomized, double-blind, placebo-controlled trial evaluating cysteamine in Huntington's disease. Movement Disorders 2017;32:932-936.
  •  Cassereau J, Ferré M, Chevrollier A, Codron P, Verny C, Homedan C, Lenaers G, Procaccio V, May-Panloup P, Reynier P. Neurotoxicity of insecticides. Current Medicinal Chemistry 2017;24:2988-3001.
  • Aung T, Ozaki M, Lee MC, Schlötzer-Schrehardt U, Thorleifsson G, Mizoguchi T, Igo RP Jr, Haripriya A, Williams SE, Astakhov YS, Orr AC, Burdon KP, Nakano S, Mori K, Abu-Amero K, Hauser M, Li Z, Prakadeeswari G, Bailey JNC, Cherecheanu AP, Kang JH, Nelson S, Hayashi K, Manabe SI, Kazama S, Zarnowski T, Inoue K, Irkec M, Coca-Prados M, Sugiyama K, Järvelä I, Schlottmann P, Lerner SF, Lamari H, Nilgün Y, Bikbov M, Park KH, Cha SC, Yamashiro K, Zenteno JC, Jonas JB, Kumar RS, Perera SA, Chan ASY, Kobakhidze N, George R, Vijaya L, Do T, Edward DP, de Juan Marcos L, Pakravan M, Moghimi S, Ideta R, Bach-Holm D, Kappelgaard P, Wirostko B, Thomas S, Gaston D, Bedard K, Greer WL, Yang Z, Chen X, Huang L, Sang J, Jia H, Jia L, Qiao C, Zhang H, Liu X, Zhao B, Wang YX, Xu L, Leruez S, Reynier P, Chichua G, Tabagari S, Uebe S, Zenkel M, Berner D, Mossböck G, Weisschuh N, Hoja U, Welge-Luessen UC, Mardin C, Founti P, Chatzikyriakidou A, Pappas T, Anastasopoulos E, Lambropoulos A, Ghosh A, Shetty R, Porporato N, Saravanan V, Venkatesh R, Shivkumar C, Kalpana N, Sarangapani S, Kanavi MR, Beni AN, Yazdani S, Lashay A, Naderifar H, Khatibi N, Fea A, Lavia C, Dallorto L, Rolle T, Frezzotti P, Paoli D, Salvi E, Manunta P, Mori Y, Miyata K, Higashide T, Chihara E, Ishiko S, Yoshida A, Yanagi M, Kiuchi Y, Ohashi T, Sakurai T, Sugimoto T, Chuman H, Aihara M, Inatani M, Miyake M, Gotoh N, Matsuda F, Yoshimura N, Ikeda Y, Ueno M, Sotozono C, Jeoung JW, Sagong M, Park KH, Ahn J, Cruz-Aguilar M, Ezzouhairi SM, Rafei A, Chong YF, Ng XY, Goh SR, Chen Y, Yong VHK, Khan MI, Olawoye OO, Ashaye AO, Ugbede I, Onakoya A, Kizor-Akaraiwe N, Teekhasaenee C, Suwan Y, Supakontanasan W, Okeke S, Uche NJ, Asimadu I, Ayub H, Akhtar F, Kosior-Jarecka E, Lukasik U, Lischinsky I, Castro V, Grossmann RP, Megevand GS, Roy S, Dervan E, Silke E, Rao A, Sahay P, Fornero P, Cuello O, Sivori D, Zompa T, Mills RA, Souzeau E, Mitchell P, Wang JJ, Hewitt AW, Coote M, Crowston JG, Astakhov SY, Akopov EL, Emelyanov A, Vysochinskaya V, Kazakbaeva G, Fayzrakhmanov R, Al-Obeidan SA, Owaidhah O, Aljasim LA, Chowbay B, Foo JN, Soh RQ, Sim KS, Xie Z, Cheong AWO, Mok SQ, Soo HM, Chen XY, Peh SQ, Heng KK, Husain R, Ho SL, Hillmer AM, Cheng CY, Escudero-Domínguez FA, González-Sarmiento R, Martinon-Torres F, Salas A, Pathanapitoon K, Hansapinyo L, Wanichwecharugruang B, Kitnarong N, Sakuntabhai A, Nguyn HX, Nguyn GTT, Nguyn TV, Zenz W, Binder A, Klobassa DS, Hibberd ML, Davila S, Herms S, Nöthen MM, Moebus S, Rautenbach RM, Ziskind A, Carmichael TR, Ramsay M, Álvarez L, García M, González-Iglesias H, Rodríguez-Calvo PP, Cueto LF, Oguz Ç, Tamcelik N, Atalay E, Batu B, Aktas D, Kasım B, Wilson MR, Coleman AL, Liu Y, Challa P, Herndon L, Kuchtey RW, Kuchtey J, Curtin K, Chaya CJ, Crandall A, Zangwill LM, Wong TY, Nakano M, Kinoshita S, den Hollander AI, Vesti E, Fingert JH, Lee RK, Sit AJ, Shingleton BJ, Wang N, Cusi D, Qamar R, Kraft P, Pericak-Vance MA, Raychaudhuri S, Heegaard S, Kivelä T, Reis A, Kruse FE, Weinreb RN, Pasquale LR, Haines JL, Thorsteinsdottir U, Jonasson F, Allingham RR, Milea D, Ritch R, Kubota T, Tashiro K, Vithana EN, Micheal S, Topouzis F, Craig JE, Dubina M, Sundaresan P, Stefansson K, Wiggs JL, Pasutto F, Khor CC. Genetic association study of exfoliation syndrome identifies a protective rare variant at LOXL1 and five new susceptibility loci. Nature Genetics 2017;49:993-1004.
  • Lim L, Palayer M, Bruneau A, Letournel F, Le Maréchal C, Simard G, Reynier P, Homedan C, Nadaj-Pakleza A. Myoadenylate deaminase deficiency: a frequent cause of muscle pain A case detected by exercise testing. Ann Biol Clin (Paris) 2017;75:445-449.
  • Charif M, Nasca A, Thompson K, Gerber S, Makowski C, Mazaheri N, Bris C, Goudenège D, Legati A, Marrofian R, Shariati G, Lamantea E, Hopton S, Ardissone A, Moroni I, Giannotta M, Siegel C, Strom TM, Prokisch H, Vignal-Clermont C, Derrien S, Zanlonghi X, Kaplan J, Hamel CP, Leruez S, Procaccio V, Bonneau D, Reynier P, White FE, Hardy SA, Barbosa IA, Simpson MA, Vara R, Perdomo Trujillo Y, Galehdari H, Deshpande C, Haack TB, Rozet JM, Taylor RW, Ghezzi D, Amati-Bonneau P, Lenaers G. Neurologic Phenotypes Associated With Mutations in RTN4IP1 (OPA10) in Children and Young Adults. JAMA Neurology 2017;75:105-113.
  • Veyrat-Durebex C, Bocca C, Chupin S, Kouassi Nzoughet J, Simard G, Lenaers G, Reynier P, Blasco H. Metabolomics and Lipidomics Profiling of a Combined Mitochondrial Plus Endoplasmic Reticulum Fraction of Human Fibroblasts: A Robust Tool for Clinical Studies. Journal of Proteome Research 2017;17:745-750.
  • Bruno C, Patin F, Bocca C, Nadal-Desbarats L, Bonnier F, Reynier P, Emond P, Vourc'h P, Joseph-Delafont K, Corcia P, Andres CR, Blasco H. The combination of four analytical methods to explore skeletal muscle metabolomics: Better coverage of metabolic pathways or a marketing argument? Journal of Pharmaceutical and Biomedical Analysis 2018;148:273-279.
  • Sarzi E, Seveno M, Angebault C, Milea D, Rönnbäck C, Quilès M, Adrian M, Grenier J, Caignard A, Lacroux A, Lavergne C, Reynier P, Larsen M, Hamel CP, Delettre C, Lenaers G, Müller A. Increased steroidogenesis promotes early-onset and severe vision loss in females with OPA1 dominant optic atrophy. Human Molecular Genetics 2017;26:4764.
  • Chao de la Barca JM, Boueilh T, Simard G, Boucret L, Ferré-L'Hotellier V, Tessier L, Gadras C, Bouet PE, Descamps P, Procaccio V, Reynier P, May-Panloup P. Targeted metabolomics reveals reduced levels of polyunsaturated choline plasmalogens and a smaller dimethylarginine/arginine ratio in the follicular fluid of patients with a diminished ovarian reserve. Human Reproduction 2017;32:2269-2278.
  • Rousseau G, Signolet I, Denis MC, Chao de la Barca JM, Mahieu R, Letournel F, Reynier P, Simard G. 5-Oxoprolinuria in hyperammonemic encephalopathy: Coincidence or worsening factor? Clinical Biochemistry 2017;50:1115-1117.
  • Gerber S, Charif M, Chevrollier A, Chaumette T, Angebault C, Kane MS, Paris A, Alban J, Quiles M, Delettre C, Bonneau D, Procaccio V, Amati-Bonneau P, Reynier P, Leruez S, Calmon R, Boddaert N, Funalot B, Rio M, Bouccara D, Meunier I, Sesaki H, Kaplan J, Hamel CP, Rozet JM, Lenaers G. Mutations in DNM1L, as in OPA1, result in dominant optic atrophy despite opposite effects on mitochondrial fusion and fission. Brain 2017;140:2586-2596.
  • Boucret L, Bris C, Seegers V, Goudenège D, Desquiret-Dumas V, Domin-Bernhard M, Ferré-L'Hotellier V, Bouet PE, Descamps P, Reynier P, Procaccio V, May-Panloup P. Deep sequencing shows that oocytes are not prone to accumulate mtDNA heteroplasmic mutations during ovarian ageing. Human Reproduction 2017;32:2101-2109.
  • Blasco H, Veyrat-Durebex C, Bocca C, Patin F, Vourc'h P, Kouassi Nzoughet J, Lenaers G, Andres CR, Simard G, Corcia P, Reynier P. Lipidomics Reveals Cerebrospinal-Fluid Signatures of ALS. Scientific Reports 2017;7:17652.
  • Bris C, Rouaud T, Desquiret-Dumas V, Gueguen N, Goudenege D, Barth M, Bonneau D, Amati-Bonneau P, Lenaers G, Reynier P, Lebre AS, Procaccio V. Novel NDUFS4 gene mutation in an atypical late-onset mitochondrial form of multifocal dystonia. Neurology Genetics 2017;3:e205. 
  • Kane MS, Paris A, Codron P, Cassereau J, Procaccio V, Lenaers G, Reynier P, Chevrollier A. Current mechanistic insights into the CCCP-induced cell survival response. Biochemical Pharmacology 2018;148:100-110.
  • Bocca C, Kouassi Nzoughet J, Leruez S, Amati-Bonneau P, Ferré M, Kane MS, Veyrat-Durebex C, Chao de la Barca JM, Chevrollier A, Homedan C, Verny C, Miléa D, Procaccio V, Simard G, Bonneau D, Lenaers G, Reynier P. A Plasma Metabolomic Signature Involving Purine Metabolism in Human Optic Atrophy 1 (OPA1)-Related Disorders. Investigative Ophthalmology and Visual Science 2018;59:185-195.
  • Codron P, Cassereau J, Vourc'h P, Veyrat-Durebex C, Blasco H, Kane S, Procaccio V, Letournel F, Verny C, Lenears G, Reynier P, Chevrollier A. Primary fibroblasts derived from sporadic amyotrophic lateral sclerosis patients do not show ALS cytological lesions. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration 2018 Janv 1:1-11.
  • Veyrat-Durebex C, Reynier P, Procaccio V, Hergesheimer R, Corcia P, Andres CR, Blasco H. How Can a Ketogenic Diet Improve Motor Function? Frontier in Molecular Neuroscience 2018;11:15.
  • Leruez S, Bresson T, Chao de la Barca JM, Marill A, de Saint Martin G, Buisset A, Muller J, Tessier L, Gadras C, Verny C, Amati-Bonneau P, Lenaers G, Gohier P, Bonneau D, Simard G, Milea D, Procaccio V, Reynier P. A Plasma Metabolomic Signature of the Exfoliation Syndrome Involves Amino Acids, Acylcarnitines, and Polyamines. Investigative Ophthalmology and Visual Science 2018;59:1025-1032.
  • Geffroy G, Benyahia R, Frey S, Desquiret-Dumas V, Gueguen N, Bris C, Belal S, Inisan A, Renaud A, Chevrollier A, Henrion D, Bonneau D, Letournel F, Lenaers G, Reynier P, Procaccio V. The accumulation of assembly intermediates of the mitochondrial complex I matrix arm is reduced by limiting glucose uptake in a neuronal-like model of MELAS syndrome. Biochimica Biophysica Acta – Molecular Basis of Diseases 2018;1864:1596-1608.
  • Leruez S, Verny C, Bonneau D, Procaccio V, Lenaers G, Amati-Bonneau P, Reynier P, Scherer C, Prundean A, Orssaud C, Zanlonghi X, Rougier MB, Tilikete C, Miléa D. Cyclosporine A does not prevent second-eye involvement in Leber's hereditary optic neuropathy. Orphanet Journal of Rare Diseases 2018;13:33.
  • Natoli R, Fernando N, Dahlenburg T, Jiao H, Aggio-Bruce R, Barnett NL, Chao de la Barca JM, Tcherkez G, Reynier P, Fang J, Chu-Tan JA, Valter K, Provis J, Rutar M. Obesity-induced metabolic disturbance drives oxidative stress and complement activation in the retinal environment. Molecular Vision 2018;24:201-217.
  • Gerber S, Charif M, Chevrollier A, Chaumette T, Angebault C, Kane S, Paris A, Alban J, Quiles M, Delettre C, Bonneau D, Procaccio V, Amati-Bonneau P, Reynier P, Leruez S, Calmon R, Boddaert N, Funalot B, Rio M, Bouccara D, Meunier I, Sesaki H, Kaplan J, Hamel CP, Rozet JM, Lenaers G. Reply: The expanding neurological phenotype of DNM1L-related disorders. Brain 2018;141:e29.
  • Rousseau G, Reynier P, Jousset N, Rougé-Maillart C, Palmiere C. Updated review of postmortem biochemical exploration of hypothermia with a presentation of standard strategy of sampling and analyses. Clinical Chemistry and Laboratory Medicine 2018 May 1. [Epub ahead of print].
  • Signolet I, Abraham P, Chupin S, Ammi M, Gueguen N, Letournel F, Picquet J, Baufreton C, Daligault M, Procaccio V, Reynier P, Henni S. Mitochondrial complex I defect resulting from exercise-induced lower-limb ischemia in patients with peripheral arterial disease. Journal of Applied Physiology (1985). 2018 May 24.
  • Rousseau G, Bergerat N, Drevin G, Reynier P, Jousset N. Thanatobiochemistry: post mortem study of the vitreous humor for the diagnosis of diabetic ketoacidosis death. Annales de Biologie Clinique (Paris). 2018;76:245-250. 
  • Belizna C, Stojanovich L, Cohen-Tervaert JW, Fassot C, Henrion D, Loufrani L, Nagy G, Muchardt C, Hasan M, Ungeheuer MN, Arnaud L, Alijotas-Reig J, Esteve-Valverde E, Nicoletti F, Saulnier P, Godon A, Reynier P, Chrétien JM, Damian L, Omarjee L, Mahé G, Pistorius MA, Meroni PL, Devreese K. Primary antiphospholipid syndrome and antiphospholipid syndrome associated to systemic lupus: Are they different entities? Autoimmunity Review 2018;17:739-745.
  • Lefebvre T, Roche O, Seegers V, Cherif M, Khiati S, Gueguen N, Desquiret-Dumas V, Geffroy G, Blanchet O, Reynier P, Legendre G, Lenaers G, Procaccio V, Gascoin G. Study of mitochondrial function in placental insufficiency. Placenta 2018;67:1-7. 
  • Najjar RP, Reynier P, Caignard A, Procaccio V, Amati-Bonneau P, Mack H, Milea D. Retinal Neuronal Loss in Visually Asymptomatic Patients With Myoclonic Epilepsy With Ragged-Red Fibers. Journal of Neuroophthalmology 2018 Jul 3. 
  • Bocca C, Kane MS, Veyrat-Durebex C, Chupin S, Alban J, Kouassi Nzoughet J, Le Mao M, Chao de la Barca JM, Amati-Bonneau P, Bonneau D, Procaccio V, Lenaers G, Simard G, Chevrollier A, Reynier P. The Metabolomic Bioenergetic Signature of Opa1-Disrupted Mouse Embryonic Fibroblasts Highlights Aspartate Deficiency. Scientific Reports 2018;8:11528.
  • Leruez S, Marill A, Bresson T, de Saint Martin G, Buisset A, Muller J, Tessier L, Gadras C, Verny C, Gohier P, Amati-Bonneau P, Lenaers G, Bonneau D, Simard G, Milea D, Procaccio V, Reynier P, Chao de la Barca JM. A Metabolomics Profiling of Glaucoma Points to Mitochondrial Dysfunction, Senescence, and Polyamines Deficiency. Investigative Ophthalmology and Visual Science 2018;59:4355-4361.
  • Rousseau G, Chao de la Barca JM, Rougé-Maillart C, Teresiński G, Jousset N, Dieu X, Chabrun F, Prunier-Mirabeau D, Simard G, Reynier P, Palmiere C. A serum metabolomics signature of hypothermia fatalities involving arginase activity, tryptophan content, and phosphatidylcholine saturation. International Journal of Legal Medicine 2018 Sep 18.
  • Taugourdeau A, Desquiret-Dumas V, Hamel JF, Chupin S, Boucret L, Ferré-L'Hotellier V, Bouet PE, Descamps P, Procaccio V, Reynier P, May-Panloup P. The mitochondrial DNA content of cumulus cells may help predict embryo implantation. Journal of Assisted Reproduction and Genetics 2018 Oct 25. 
  • Goudenège D, Bris C, Hoffmann V, Desquiret-Dumas V, Jardel C, Rucheton B, Bannwarth S, Paquis-Flucklinger V, Lebre AS, Colin E, Amati-Bonneau P, Bonneau D, Reynier P, Lenaers G, Procaccio V. eKLIPse: a sensitive tool for the detection and quantification of mitochondrial DNA deletions from next-generation sequencing data. Genetics in Medicine 2018 Nov 5.
  • Felhi R, Sfaihi L, Charif M, Desquiret-Dumas V, Bris C, Goudenège D, Ammar-Keskes L, Hachicha M, Bonneau D, Procaccio V, Reynier P, Amati-Bonneau P, Lenaers G, Fakhfakh F. Next generation sequencing in family with MNGIE syndrome associated to optic atrophy: Novel homozygous POLG mutation in the C-terminal sub-domain leading to mtDNA depletion. Clinica Chimica Acta 2018 Nov 3;488:104-110.

Acknowledgements for the financial supports

  • Union National des Aveugles et Déficients Visuels (UNADEV)
  • Ouvrir les Yeux (OLY)
  • Fondation VISIO
  • Kjer France
  • Point de Mire
  • Retina France

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