p66Shc, oxidative stress and aging: importing a lifespan determinant into mitochondria.
The 66 KDa isoform of Shc and its signalling properties have attracted in the past years major interest in aging research. Here, we summarize p66Shc functions and outline a specific signalling route leading to mitochondrial import, that accounts for its pro-apoptotic activity upon oxidative stress. This model, that could explain the alterations of mitochondrial Ca2+ homeostasis observed after oxidative stress, highlights novel pharmacological targets in age-related disorders.
Pinton
Paolo
P
Department of Experimental and Diagnostic Medicine, Section of General Pathology, ER-GenTech Laboratory and Interdisciplinary Center for the Study of Inflammation (ICSI), University of Ferrara, Ferrara, Italy.
Rizzuto
Rosario
R
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016922:Cellular Senescence / Q000235:genetics / Q000502:physiology; D006801:Humans; D008136:Longevity / Q000235:genetics / Q000502:physiology*; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology*; D021381:Protein Transport / Q000235:genetics / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1
D048868:Adaptor Proteins, Signal Transducing; D017382:Reactive Oxygen Species; C528024:SHC1 protein, human; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1