title: Protein sequences involved in the mitochondrial import of the 3,5,3'-L-triiodothyronine receptor p43.
abstract: The major effect of T3 on mitochondrial activity has been partly explained by the discovery of p43, a T3-dependent transcription factor of the mitochondrial genome. P43 is imported into mitochondria in an atypical manner which is not yet fully understood. Our aim was to characterize the p43 sequences inducing its mitochondrial import, using in organello import experiments with wild-type or mutated proteins and validation in CV1 cells. We find that several sequences define the mitochondrial addressing. Two alpha helices in the C-terminal part of p43 are actual mitochondrial import sequences as fusion to a cytosolic protein induces its mitochondrial translocation. Helix 5 drives the atypical mitochondrial import process, whereas helices 10/11 induce a classical import process. However, despite its inability to drive a mitochondrial import, the N-terminal region of p43 also plays a permissive role as in the presence of the C-terminal import sequences different N-terminal regions determine whether the protein is imported or not. These results can be extrapolated to other mitochondrial proteins related to the nuclear receptor superfamily, devoid of classical mitochondrial import sequences.
authors.affiliation: UMR 866 Dynamique Musculaire et Métabolisme (INRA, Université Montpellier 1, Université Montpellier 2), INRA, Montpellier cedex, France.
authors.forename: Angel
authors.initials: A
authors.lastname: Carazo
authors.forename: Jonathan
authors.initials: J
authors.lastname: Levin
authors.forename: François
authors.initials: F
authors.lastname: Casas
authors.forename: Pascal
authors.initials: P
authors.lastname: Seyer
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Grandemange
authors.forename: Muriel
authors.initials: M
authors.lastname: Busson
authors.forename: Laurence
authors.initials: L
authors.lastname: Pessemesse
authors.forename: Chantal
authors.initials: C
authors.lastname: Wrutniak-Cabello
authors.forename: Gérard
authors.initials: G
authors.lastname: Cabello
mesh_terms: D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism*; D009154:Mutation; D010957:Plasmids; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D037021:Thyroid Hormone Receptors alpha / Q000737:chemistry* / Q000378:metabolism*; D014284:Triiodothyronine / Q000378:metabolism*
chemical_list: D037021:Thyroid Hormone Receptors alpha; D014284:Triiodothyronine