title: TMEM126A is a mitochondrial located mRNA (MLR) protein of the mitochondrial inner membrane.
abstract: BACKGROUND
  Hereditary optic neuropathies (HONs) are a heterogeneous group of disorders that affect retinal ganglion cells (RGCs) and axons that form the optic nerve. Leber's Hereditary Optic Neuropathy and the autosomal dominant optic atrophy related to OPA1 mutations are the most common forms. Nonsyndromic autosomal recessive optic neuropathies are rare and their existence has been long debated. We recently identified the first gene responsible for these conditions, TMEM126A. This gene is highly expressed in retinal cellular compartments enriched in mitochondria and supposed to encode a mitochondrial transmembrane protein of unknown function.
  
  
  METHODS
  A specific polyclonal antibody targeting the TMEM126A protein has been generated. Quantitative fluorescent in situ hybridization, cellular fractionation, mitochondrial membrane association study, mitochondrial sub compartmentalization analysis by both proteolysis assays and transmission electron microscopy, and expression analysis of truncated TMEM126A constructs by immunofluorescence confocal microscopy were carried out.
  
  
  RESULTS
  TMEM126A mRNAs are strongly enriched in the vicinity of mitochondria and encode an inner mitochondrial membrane associated cristae protein. Moreover, the second transmembrane domain of TMEM126A is required for its mitochondrial localization.
  
  
  CONCLUSIONS
  TMEM126A is a mitochondrial located mRNA (MLR) that may be translated in the mitochondrial surface and the protein is subsequently imported to the inner membrane. These data constitute the first step toward a better understanding of the mechanism of action of TMEM126A in RGCs and support the importance of mitochondrial dysfunction in the pathogenesis of HON.
  
  
  CONCLUSIONS
  Local translation of nuclearly encoded mitochondrial mRNAs might be a mechanism for rapid onsite supply of mitochondrial membrane proteins.
authors.affiliation: Départment de Génétique, Fondation Imagine, Université Paris Descartes-Sorbonne Paris Cité, Paris, France. sylvainhanein@hotmail.com
authors.forename: Sylvain
authors.initials: S
authors.lastname: Hanein
authors.forename: Mathilde
authors.initials: M
authors.lastname: Garcia
authors.forename: Lucas
authors.initials: L
authors.lastname: Fares-Taie
authors.forename: Valérie
authors.initials: V
authors.lastname: Serre
authors.forename: Yves
authors.initials: Y
authors.lastname: De Keyzer
authors.forename: Thierry
authors.initials: T
authors.lastname: Delaveau
authors.forename: Isabelle
authors.initials: I
authors.lastname: Perrault
authors.forename: Nathalie
authors.initials: N
authors.lastname: Delphin
authors.forename: Sylvie
authors.initials: S
authors.lastname: Gerber
authors.forename: Alain
authors.initials: A
authors.lastname: Schmitt
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Masse
authors.forename: Arnold
authors.initials: A
authors.lastname: Munnich
authors.forename: Josseline
authors.initials: J
authors.lastname: Kaplan
authors.forename: Frédéric
authors.initials: F
authors.lastname: Devaux
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Rozet
mesh_terms: D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism; D030342:Genetic Diseases, Inborn / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D051336:Mitochondrial Membranes / Q000378:metabolism* / Q000473:pathology; D024101:Mitochondrial Proteins / Q000096:biosynthesis* / Q000235:genetics; D009154:Mutation; D009901:Optic Nerve Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000378:metabolism* / Q000473:pathology
chemical_list: D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; C549198:TMEM126A protein, human; D020558:GTP Phosphohydrolases; C415198:OPA1 protein, human