Impairment of F1F0-ATPase, adenine nucleotide translocator and adenylate kinase causes mitochondrial energy deficit in human skin fibroblasts with chromosome 21 trisomy (Articolo in rivista)

Type
Label
  • Impairment of F1F0-ATPase, adenine nucleotide translocator and adenylate kinase causes mitochondrial energy deficit in human skin fibroblasts with chromosome 21 trisomy (Articolo in rivista) (literal)
Anno
  • 2010-01-01T00:00:00+01:00 (literal)
Alternative label
  • Valenti D, Tullo A, Caratozzolo MF, Merafina RS, Scartezzini P, Marra E, Vacca RA. (2010)
    Impairment of F1F0-ATPase, adenine nucleotide translocator and adenylate kinase causes mitochondrial energy deficit in human skin fibroblasts with chromosome 21 trisomy
    in Biochemical journal (Lond., 1984)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Valenti D, Tullo A, Caratozzolo MF, Merafina RS, Scartezzini P, Marra E, Vacca RA. (literal)
Pagina inizio
  • 299 (literal)
Pagina fine
  • 310 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 431 (literal)
Rivista
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Institute of Biomembranes and Bioenergetics, National Research Council (CNR), 70126 Bari, Italy. Institute for Biomedical Technologies, National Research Council (CNR), 70126 Bari, Italy. Department of Gerontology and Motor Sciences, Galliera Hospitals, 16128 Genova, Italy. (literal)
Titolo
  • Impairment of F1F0-ATPase, adenine nucleotide translocator and adenylate kinase causes mitochondrial energy deficit in human skin fibroblasts with chromosome 21 trisomy (literal)
Abstract
  • A central role for mitochondrial dysfunctions has been proposed in the pathogenesis of Down syndrome (DS), a multifactorial disorder caused by trisomy of human chromosome 21. To explore whether and how abnormalities in mitochondrial energy metabolism are involved in DS pathogenesis, we investigated the catalytic properties, gene expression and protein levels of certain proteins involved in mitochondrial ATP synthesis such as ATPase, ADP/ATP translocator (ANT) and adenylate kinase (AK) in human skin fibroblasts from subjects with DS (DS-HSF) comparing them with euploid fibroblasts. In DS-HSF, we found a strong impairment of mitochondrial ATP synthesis due to a reduction in the catalytic efficiency of each of the investigated proteins. This impairment occurred in spite of unchanged gene expression and an increase in ANT and AK protein content, whereas the amount of ATPase subunits was selectively reduced. Interestingly, exposure of DS-HSF to dibutyryl-cAMP, a permanent derivative of cAMP, stimulated ANT, AK and ATPase activities whereas H89, a specific PKA inhibitor, suppressed this cAMP-dependent activation, indicating an involvement of cAMP/PKA-mediated signalling pathway in ATPase, ANT and AK deficit. Consistently, DS-HSF showed decreased basal levels of cAMP and reduced PKA activity. Despite the impairment of mitochondrial energy apparatus, no changes in cellular energy status but increased basal levels of L-lactate were found in DS-HSF which partially offset for mitochondrial energy deficit by increasing glycolysis and mitochondrial mass. These results give new insight into the molecular basis for mitochondrial dysfunction in DS and might provide a molecular explanation for some clinical features of the syndrome. (literal)
Prodotto di
Autore CNR
Insieme di parole chiave

Incoming links:


Prodotto
Autore CNR di
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#rivistaDi
Insieme di parole chiave di
data.CNR.it