title: Bovine and murine models highlight novel roles for SLC25A46 in mitochondrial dynamics and metabolism, with implications for human and animal health.
abstract: Neuropathies are neurodegenerative diseases affecting humans and other mammals. Many genetic causes have been identified so far, including mutations of genes encoding proteins involved in mitochondrial dynamics. Recently, the "Turning calves syndrome", a novel sensorimotor polyneuropathy was described in the French Rouge-des-Prés cattle breed. In the present study, we determined that this hereditary disease resulted from a single nucleotide substitution in SLC25A46, a gene encoding a protein of the mitochondrial carrier family. This mutation caused an apparent damaging amino-acid substitution. To better understand the function of this protein, we knocked out the Slc25a46 gene in a mouse model. This alteration affected not only the nervous system but also altered general metabolism, resulting in premature mortality. Based on optic microscopy examination, electron microscopy and on biochemical, metabolic and proteomic analyses, we showed that the Slc25a46 disruption caused a fusion/fission imbalance and an abnormal mitochondrial architecture that disturbed mitochondrial metabolism. These data extended the range of phenotypes associated with Slc25a46 dysfunction. Moreover, this Slc25a46 knock-out mouse model should be useful to further elucidate the role of SLC25A46 in mitochondrial dynamics.
authors.affiliation: GABI, INRA, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, France.
authors.forename: Amandine
authors.identifier: 0000-0002-9713-2274
authors.initials: A
authors.lastname: Duchesne
authors.affiliation: GABI, INRA, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Vaiman
authors.affiliation: GABI, INRA, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, France.
authors.forename: Johan
authors.identifier: 0000-0001-5388-9374
authors.initials: J
authors.lastname: Castille
authors.affiliation: GABI, INRA, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Beauvallet
authors.affiliation: Biochemistry Laboratory, Bicêtre Hospital, Assistance-Publique Hôpitaux de Paris, University Paris-Sud, Le Kremlin-Bicêtre Cedex, France.
authors.forename: Pauline
authors.identifier: 0000-0002-9520-2013
authors.initials: P
authors.lastname: Gaignard
authors.affiliation: GABI, INRA, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Floriot
authors.affiliation: GABI, INRA, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, France.|TWB, Université de Toulouse, INRA, INSA, CNRS, Ramonville Saint-Agne, France.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Rodriguez
authors.affiliation: GABI, INRA, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, France.
authors.forename: Marthe
authors.initials: M
authors.lastname: Vilotte
authors.affiliation: UMR BDR, INRA, ENVA, Université Paris Saclay, Jouy en Josas, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Boulanger
authors.affiliation: GABI, INRA, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, France.
authors.forename: Bruno
authors.identifier: 0000-0001-5262-0314
authors.initials: B
authors.lastname: Passet
authors.affiliation: LHA, Oniris, Nantes Atlantic College of Veterinary Medecine, Food Science and Engineering, Université Nantes Angers Le Mans, Nantes, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Albaric
authors.affiliation: GABI, INRA, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, France.
authors.forename: François
authors.initials: F
authors.lastname: Guillaume
authors.affiliation: GABI, INRA, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, France.
authors.forename: Abdelhak
authors.initials: A
authors.lastname: Boukadiri
authors.affiliation: Department of Neurology, National Reference Center for Rare Peripheral Neuropathies, University Hospital, Limoges, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Richard
authors.affiliation: GABI, INRA, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, France.
authors.forename: Maud
authors.initials: M
authors.lastname: Bertaud
authors.affiliation: Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, Canada.
authors.forename: Edouard
authors.initials: E
authors.lastname: Timsit
authors.affiliation: BIOEPAR, INRA, Oniris, Nantes, France.
authors.forename: Raphaël
authors.initials: R
authors.lastname: Guatteo
authors.affiliation: GABI, INRA, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Jaffrézic
authors.affiliation: GABI, INRA, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Calvel
authors.affiliation: GABI, INRA, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, France.
authors.forename: Louise
authors.initials: L
authors.lastname: Helary
authors.affiliation: Labogena, Jouy-en-Josas, France.
authors.forename: Rachid
authors.initials: R
authors.lastname: Mahla
authors.affiliation: GenPhySE, Université de Toulouse, INRA, INPT, ENVT, Castanet Tolosan, France.
authors.forename: Diane
authors.initials: D
authors.lastname: Esquerré
authors.affiliation: GABI, INRA, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Péchoux
authors.affiliation: Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Liuu
authors.affiliation: Department of Neurology, National Reference Center for Rare Peripheral Neuropathies, University Hospital, Limoges, France.
authors.forename: Jean-Michel
authors.identifier: 0000-0002-9713-2274
authors.initials: JM
authors.lastname: Vallat
authors.affiliation: GABI, INRA, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Boichard
authors.affiliation: Biochemistry Laboratory, Bicêtre Hospital, Assistance-Publique Hôpitaux de Paris, University Paris-Sud, Le Kremlin-Bicêtre Cedex, France.
authors.forename: Abdelhamid
authors.initials: A
authors.lastname: Slama
authors.affiliation: GABI, INRA, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Vilotte
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D002417:Cattle; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000235:genetics / Q000473:pathology; D063154:Mitochondrial Dynamics / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D028061:Phosphate Transport Proteins / Q000235:genetics*; D011115:Polyneuropathies / Q000235:genetics* / Q000473:pathology / Q000662:veterinary; D040901:Proteomics
chemical_list: D024101:Mitochondrial Proteins; D028061:Phosphate Transport Proteins; C584459:SLC25A46 protein, human