Bovine and murine models highlight novel roles for SLC25A46 in mitochondrial dynamics and metabolism, with implications for human and animal health

• DOI: 10.1371/journal.pgen.1006597
• Publication Date: 2017-04-04T22:04:42Z
• Authors: Amandine Duchesne; Anne Vaiman; Johan Castille; Christian Beauvallet; Pauline Gaignard; Sandrine Floriot; Sabrina Rodriguez; Marthe Vilotte; Laurent Boulanger; Bruno Passet; Olivier Albaric; François Guillaume; Abdelhak Boukadiri; Laurence Richard; Maud Bertaud; Edouard Timsit; Raphaël Guatteo; Florence Jaffrézic; Pierre Calvel; Louise Helary; Rachid Mahla; Diane Esquerré; Christine Péchoux; Sophie Liuu; Jean-Michel Vallat; Didier Boichard; Abdelhamid Slama; Jean-Luc Vilotte
• Keywords: MFN2

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 French Rouge-des-Prés cattle breed. In present study, we determined that this hereditary disease resulted from single nucleotide substitution SLC25A46, gene protein carrier family. This mutation caused an apparent damaging amino-acid substitution. To better understand function protein, knocked out Slc25a46 mouse model. alteration affected not only nervous system but also altered general metabolism, resulting premature mortality. Based on optic microscopy examination, electron biochemical, metabolic proteomic analyses, showed disruption fusion/fission imbalance abnormal architecture disturbed metabolism. These data extended range phenotypes associated with dysfunction. Moreover, knock-out model should be useful to further elucidate role SLC25A46