Neuronal nitric-oxide synthase (nNOS) has various splicing variants and different subcellular localizations. nNOS can be found also in the nucleus; however, its exact role in this compartment is still not completely defined. In this report, we demonstrate that the PDZ domain allows the recruitment of nNOS to nuclei, thus favoring local NO production, nuclear protein S-nitrosylation, and induction of mitochondrial biogenesis. In particular, overexpression of PDZ-containing nNOS (nNOS) increases S-nitrosylated CREB with consequent augmented binding on cAMP response element consensus sequence on peroxisome proliferator-activated receptor co-activator (PGC)-1 promoter. The resulting PGC-1 induction is accompanied by the expression of mitochondrial genes (e.g., TFAM, MtCO1) and increased mitochondrial mass. Importantly, full active nNOS lacking PDZ domain (nNOS) does not localize in nuclei and fails in inducing the expression of PGC-1. Moreover, we substantiate that the mitochondrial biogenesis normally accompanying myogenesis is associated with nuclear translocation of nNOS. We demonstrate that -Syntrophin, which resides in nuclei of myocytes, functions as the upstream mediator of nuclear nNOS translocation and nNOS-dependent mitochondrial biogenesis. Overall, our results indicate that altered nNOS splicing and nuclear localization could be contributing factors in human muscular diseases associated with mitochondrial impairment.

Aquilano, K., Baldelli, S., Ciriolo, M.r. (2014). Nuclear Recruitment of Neuronal Nitric-oxide Synthase by alpha-Syntrophin Is Crucial for the Induction of Mitochondrial Biogenesis. THE JOURNAL OF BIOLOGICAL CHEMISTRY, 289(1), 365-378 [10.1074/jbc.M113.506733].

Nuclear Recruitment of Neuronal Nitric-oxide Synthase by alpha-Syntrophin Is Crucial for the Induction of Mitochondrial Biogenesis

AQUILANO, KATIA;CIRIOLO, MARIA ROSA
2014-01-01

Abstract

Neuronal nitric-oxide synthase (nNOS) has various splicing variants and different subcellular localizations. nNOS can be found also in the nucleus; however, its exact role in this compartment is still not completely defined. In this report, we demonstrate that the PDZ domain allows the recruitment of nNOS to nuclei, thus favoring local NO production, nuclear protein S-nitrosylation, and induction of mitochondrial biogenesis. In particular, overexpression of PDZ-containing nNOS (nNOS) increases S-nitrosylated CREB with consequent augmented binding on cAMP response element consensus sequence on peroxisome proliferator-activated receptor co-activator (PGC)-1 promoter. The resulting PGC-1 induction is accompanied by the expression of mitochondrial genes (e.g., TFAM, MtCO1) and increased mitochondrial mass. Importantly, full active nNOS lacking PDZ domain (nNOS) does not localize in nuclei and fails in inducing the expression of PGC-1. Moreover, we substantiate that the mitochondrial biogenesis normally accompanying myogenesis is associated with nuclear translocation of nNOS. We demonstrate that -Syntrophin, which resides in nuclei of myocytes, functions as the upstream mediator of nuclear nNOS translocation and nNOS-dependent mitochondrial biogenesis. Overall, our results indicate that altered nNOS splicing and nuclear localization could be contributing factors in human muscular diseases associated with mitochondrial impairment.
2014
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/10 - BIOCHIMICA
Settore MED/49 - SCIENZE TECNICHE DIETETICHE APPLICATE
English
Con Impact Factor ISI
Aquilano, K., Baldelli, S., Ciriolo, M.r. (2014). Nuclear Recruitment of Neuronal Nitric-oxide Synthase by alpha-Syntrophin Is Crucial for the Induction of Mitochondrial Biogenesis. THE JOURNAL OF BIOLOGICAL CHEMISTRY, 289(1), 365-378 [10.1074/jbc.M113.506733].
Aquilano, K; Baldelli, S; Ciriolo, Mr
Articolo su rivista
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/97230
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 46
  • ???jsp.display-item.citation.isi??? 43
social impact