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Citation
Baqri, R.M., Pietron, A.V., Gokhale, R.H., Turner, B.A., Kaguni, L.S., Shingleton, A.W., Kunes, S., Miller, K.E. (2014). Mitochondrial chaperone TRAP1 activates the mitochondrial UPR and extends healthspan in Drosophila.  Mech. Ageing Dev. 141-142(): 35--45.
FlyBase ID
FBrf0227403
Publication Type
Research paper
Abstract

The molecular mechanisms influencing healthspan are unclear but mitochondrial function, resistance to oxidative stress and proteostasis are recurring themes. Tumor necrosis factor Receptor Associated Protein 1 (TRAP1), the mitochondrial analog of Hsp75, regulates levels of reactive oxygen species in vitro and is found expressed at higher levels in tumor cells where it is thought to play a pro-survival role. While TRAP1-directed compartmentalized protein folding is a promising target for cancer therapy, its role at the organismal level is unclear. Here we report that overexpression of TRAP1 in Drosophila extends healthspan by enhancing stress resistance, locomotor activity and fertility while depletion of TRAP1 has the opposite effect, with little effect on lifespan under both conditions. In addition, modulating TRAP1 expression promotes the nuclear translocation of homeobox protein Dve and increases expression of genes associated with the mitochondrial unfolded protein response (UPR(mt)), indicating an activation of this proteostasis pathway. Notably, independent genetic knockdown of components of the UPR(mt) pathway dampen the enhanced stress resistance observed in TRAP1 overexpression flies. Together these studies suggest that TRAP1 regulates healthspan, potentially through activation of the UPR(mt).

PubMed ID
PubMed Central ID
PMC4310785 (PMC) (EuropePMC)
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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Mech. Ageing Dev.
    Title
    Mechanisms of Ageing and Development
    Publication Year
    1972-
    ISBN/ISSN
    0047-6374
    Data From Reference
    Alleles (7)
    Genes (6)
    Natural transposons (1)
    Insertions (2)
    Experimental Tools (1)
    Transgenic Constructs (6)