Expression of human uncoupling protein-3 in insulin-producing cells increases insulin-like peptide (DILP) levels and shortens lifespan - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Experimental Gerontology Année : 2009

Expression of human uncoupling protein-3 in insulin-producing cells increases insulin-like peptide (DILP) levels and shortens lifespan

Dickon M. Humphrey
  • Fonction : Auteur
Janne M. Toivonen
  • Fonction : Auteur
Maria Giannakou
  • Fonction : Auteur
Linda Partridge
  • Fonction : Auteur
Martin D. Brand
  • Fonction : Auteur correspondant
  • PersonId : 872259

Connectez-vous pour contacter l'auteur

Résumé

Uncoupling proteins (UCPs) can dissipate mitochondrial protonmotive force by increasing the proton conductance of the inner membrane and through this effect could decrease ROS production, ameliorate oxidative stress and extend lifespan. We investigated whether ubiquitous, pan-neuronal or neurosecretory cell-specific expression of human UCP3 (hUCP3) in adult affected lifespan. Low, ubiquitous expression of hUCP3 at levels found in rodent skeletal muscle mitochondria did not affect proton conductance in mitochondria isolated from whole flies, but high pan-neuronal expression of hUCP3 increased the proton conductance of mitochondria isolated from fly heads. Expression of hUCP3 at moderate levels in adult neurons led to a marginal lifespan-extension in males. However, high expression of hUCP3 in neuronal tissue shortened lifespan. The life-shortening effect was replicated when hUCP3 was expressed specifically in median neurosecretory cells (mNSC), which express three of the insulin-like peptides (DILPs). Expression of hUCP3 in the mNSC did not alter expression of mRNA, but led to increased amounts of DILP2 in fly heads. These data suggest that lowering mitochondrial coupling by high expression of hUCP3 alters mNSC function in a way that appears to increase DILP-levels in fly heads and lead to a concomitant decrease in lifespan.
Fichier principal
Vignette du fichier
PEER_stage2_10.1016%2Fj.exger.2009.02.001.pdf (632.07 Ko) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)
Loading...

Dates et versions

hal-00493097 , version 1 (18-06-2010)

Identifiants

Citer

Dickon M. Humphrey, Janne M. Toivonen, Maria Giannakou, Linda Partridge, Martin D. Brand. Expression of human uncoupling protein-3 in insulin-producing cells increases insulin-like peptide (DILP) levels and shortens lifespan. Experimental Gerontology, 2009, 44 (5), pp.316. ⟨10.1016/j.exger.2009.02.001⟩. ⟨hal-00493097⟩

Collections

PEER
28 Consultations
42 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More