Nuclear-mitochondrial shuttling of the Hsp90-binding immunophilin FKBP51

ZGAJNAR, NR; CIUCCI, SM; MAZAIRA GI,; GALIGNIANA MD

JOURNAL OF CELLULAR BIOCHEMISTRY

WILEY-LISS, DIV JOHN WILEY & SONS INC

Lugar: New York; Año: 2022

0730-2312

FKBP51 shows dynamic changes of expression and subcellular distribution, shuttling from mitochondria to the nucleus at the onset of adipocyte differentiation and later on cycling back to mitochondria. FKBP51 subcellular redistribution depends on the activation of cAMP-PKA signaling pathway. Nuclear FKBP51 shows and increased interaction with GR and this may constitute a mechanism to restrain the glucocorticoid response mediated by GR at the onset of adipogenesis.The dynamic FKBP51 mitochondrial-nuclear shuttling during the process of adipocyte differentiation dependent on PKA signaling pathway may play a key role in the control of the expression of GR-target genes required for the acquisition of the adipocyte phenotype.This is the first time that a dynamic event of mitochondrial-nuclear redistribution dependent on PKA signaling pathway is described during a process of cell differentiation. Importantly, our study provides evidence that PKA may play a dual role in the regulation of GR. It was previously reported that PKA-c potentiates GR-dependent transcription, and in the present study we show that c-AMP-PKA restrains GR transcriptional capacity by promoting the mitochondrial –nuclear relocalization of FKBP51.