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Endocrine regulation of mitochondrial activity: involvement of truncated RXR and c-Erb A1 proteins

FRANÇOIS CASAS^*, LAETITIA DAURY^*, STÉPHANIE GRANDEMANGE^*, MURIEL BUSSON^*, PASCAL SEYER^*, RENÉE HATIER, ANGEL CARAZO^*, GÉRARD CABELLO^*1 and CHANTAL WRUTNIAK-CABELLO^*

^* 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; and
EMI INSERM 0014, Laboratoire de Microscopie Electronique, Faculté de Médecine, BP 184, 54505 Vandoeuvre-lès-Nancy Cedex, France

¹Correspondence: UMR-866 Différenciation Cellulaire et Croissance, Unité d’Endocrinologie Cellulaire, Institut National de la Recherche Agronomique, 2 place Viala, 34060 Montpellier Cedex 1, France. E-mail: cabello{at}ensam.inra.fr

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 RXR (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 RXR 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.—Casas, F., Daury, L., Grandemange, S., Busson, M., Seyer, P., Hatier, R., Carazo, A., Cabello, G., Wrutniak-Cabello, C. Endocrine regulation of mitochondrial activity: involvement of truncated RXR and c-Erb A1 proteins.

Key Words: mitochondrial import • mitochondrial transcription • mt-DNA • triiodothyronine • 9-cis-retinoic acid

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