title: Endocrine regulation of mitochondrial activity: involvement of truncated RXRalpha and c-Erb Aalpha1 proteins.
abstract: The importance of mitochondrial activity has recently been extended to the regulation of developmental processes. Numerous pathologies associated with organelle's dysfunctions emphasize their physiological importance. However, regulation of mitochondrial genome transcription, a key element for organelle's function, remains poorly understood. After characterization in the organelle of a truncated form of the triiodothyronine nuclear receptor (p43), a T3-dependent transcription factor of the mitochondrial genome, our purpose was to search for other mitochondrial receptors involved in the regulation of organelle transcription. We show that a 44 kDa protein related to RXRalpha (mt-RXR), another nuclear receptor, is located in the mitochondrial matrix. We found that mt-RXR is produced after cytosolic or intramitochondrial enzymatic cleavage of the RXRalpha nuclear receptor. After mitochondrial import and binding to specific sequences of the organelle genome, mt-RXR induces a ligand-dependent increase in mitochondrial RNA levels. mt-RXR physically interacts with p43 and acts alone or through a heterodimerical complex activated by 9-cis-retinoic acid and T3 to increase RNA levels. These data indicate that hormonal regulation of mitochondrial transcription occurs through pathways similar to those that take place in the nucleus and open a new way to better understand hormone and vitamin action at the cellular level.
authors.affiliation: UMR-866 Différenciation Cellulaire et Croissance (INRA-UMII-ENSAM), Unité d'Endocrinologie Cellulaire, Institut National de la Recherche Agronomique (INRA), 34060 Montpellier Cedex 1, France.
authors.forename: François
authors.initials: F
authors.lastname: Casas
authors.forename: Laetitia
authors.initials: L
authors.lastname: Daury
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Grandemange
authors.forename: Muriel
authors.initials: M
authors.lastname: Busson
authors.forename: Pascal
authors.initials: P
authors.lastname: Seyer
authors.forename: Renée
authors.initials: R
authors.lastname: Hatier
authors.forename: Angel
authors.initials: A
authors.lastname: Carazo
authors.forename: Gérard
authors.initials: G
authors.lastname: Cabello
authors.forename: Chantal
authors.initials: C
authors.lastname: Wrutniak-Cabello
mesh_terms: D000077556:Alitretinoin; D000818:Animals; D001665:Binding Sites; D002154:Calpain / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016678:Genome; D008024:Ligands; D008297:Male; D008928:Mitochondria / Q000235:genetics*; D008930:Mitochondria, Liver / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D008954:Models, Biological; D021381:Protein Transport; D012313:RNA / Q000096:biosynthesis; D000077278:RNA, Mitochondrial; D051381:Rats; D017208:Rats, Wistar; D018168:Receptors, Retinoic Acid / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D047488:Retinoid X Receptors; D037021:Thyroid Hormone Receptors alpha / Q000737:chemistry* / Q000502:physiology*; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic; D014212:Tretinoin / Q000494:pharmacology; D014284:Triiodothyronine / Q000494:pharmacology
chemical_list: D004272:DNA, Mitochondrial; D008024:Ligands; D000077278:RNA, Mitochondrial; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D037021:Thyroid Hormone Receptors alpha; D014157:Transcription Factors; D014284:Triiodothyronine; D000077556:Alitretinoin; D014212:Tretinoin; D012313:RNA; D002154:Calpain