INIGEM   23989
INSTITUTO DE INMUNOLOGIA, GENETICA Y METABOLISMO
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
The role of p66sch in mitochondrial homeostasis during aging.
Autor/es:
PEREZ H, ELGUERO ME, ALIPPE Y, REBAGLIATI I, VILLALBA NM, PODEROSO JJ, CARRERAS MC
Lugar:
Berlin
Reunión:
Congreso; 6th World Congress on Targeting Mitochondria 2015; 2015
Resumen:
    According to the freeradicals aging theory, this process is due to accumulated oxidative damagecaused by ROS generated during mitochondrial respiration. p66shc is a longevitygenetic determinant that regulates apoptosis and metabolism through ROS generation.Our objective is to assess p66shc function on mitochondrial metabolism andphysiology during the aging process. To this aim, we explored oxidativemetabolism in brain and liver mitochondria of 3-24-month-old WT and KO mice forp66shc (p66shc-/-). We observed that p66shc-/- mouse, with longer lifeexpectancy, exhibits changes in mitochondrial function throughout aging, suchas decreased activity in the respiratory chain complexes, a reduction in H2O2production rate, elevated ATP levels and a higher NAD /NADH ratio. P66shc-/-mice have difficulty gaining weight, which is shown by a 25% body weightreduction. All these conditions trigger proliferation and delay apoptosis usingmechanisms such as mitochondrial biogenesis and dynamics. WB and qPCR showedregulation of proteins expression related to the mitochondrial fusion/fissionand biogenesis such as Drp1, Opa1, Mfn2 and PGC1a during aging in KO mice. Weconclude that the metabolic rate reduction in p66shc mice improvesmitochondrial homeostasis coordinating mitochondrial biogenesis and thefusion/fission balance. This corresponds with a delay in the aging process