Sat, 26 Jul 2008 16:57:46 BST CiteULike: carmenv Criollo http://www.citeulike.org/user/carmenv/author/Criollo CiteULike.org en-gb Copyright © 2004-2008 citeulike.org http://www.citeulike.org/user/carmenv/article/2776554 <i>Gerontology, Vol. 54, No. 2. (2008), pp. 92-99.</i><br /><br />Many features of aging result from the incapacity of cells to adapt to stress conditions. When damage accumulates irreversibly, mitotic cells from renewable tissues rely on either of two mechanisms to avoid replication. They can permanently arrest the cell cycle (cellular senescence) or trigger cell death programs. Apoptosis (self-killing) is the best-described form of programmed cell death, but autophagy (self-eating), which is a lysosomal degradation pathway essential for homeostasis, reportedly contributes to cell death as well. Unlike mitotic cells, postmitotic cells like neurons or cardiomyocytes cannot become senescent since they are already terminally differentiated. The fate of these cells entirely depends on their ability to cope with stress. Autophagy then operates as a major homeostatic mechanism to eliminate damaged organelles, long-lived or aberrant proteins and superfluous portions of the cytoplasm. In this mini-review, we briefly summarize the molecular networks that allow damaged cells either to adapt to stress or to engage in programmed-cell-death pathways. Senescence, apoptosis or autophagy? When a damaged cell must decide its path--a mini-review. JM Vicencio L Galluzzi N Tajeddine C Ortiz A Criollo E Tasdemir E Morselli A Ben Younes MC Maiuri S Lavandero G Kroemer doi:10.1159/000129697 Gerontology, Vol. 54, No. 2. (2008), pp. 92-99. 2008-05-09T20:17:30-00:00 2008 Gerontology 1423-0003 54 2 92 99 autophagy http://www.citeulike.org/user/carmenv/article/2776550 <i>Nature cell biology (4 May 2008)</i><br /><br />Multiple cellular stressors, including activation of the tumour suppressor p53, can stimulate autophagy. Here we show that deletion, depletion or inhibition of p53 can induce autophagy in human, mouse and nematode cells subjected to knockout, knockdown or pharmacological inhibition of p53. Enhanced autophagy improved the survival of p53-deficient cancer cells under conditions of hypoxia and nutrient depletion, allowing them to maintain high ATP levels. Inhibition of p53 led to autophagy in enucleated cells, and cytoplasmic, not nuclear, p53 was able to repress the enhanced autophagy of p53(-/-) cells. Many different inducers of autophagy (for example, starvation, rapamycin and toxins affecting the endoplasmic reticulum) stimulated proteasome-mediated degradation of p53 through a pathway relying on the E3 ubiquitin ligase HDM2. Inhibition of p53 degradation prevented the activation of autophagy in several cell lines, in response to several distinct stimuli. These results provide evidence of a key signalling pathway that links autophagy to the cancer-associated dysregulation of p53. Regulation of autophagy by cytoplasmic p53. Ezgi Tasdemir M Chiara Maiuri Lorenzo Galluzzi Ilio Vitale Mojgan Djavaheri-Mergny Marcello D'Amelio Alfredo Criollo Eugenia Morselli Changlian Zhu Francis Harper Ulf Nannmark Chrysanthi Samara Paolo Pinton José Miguel Vicencio Rosa Carnuccio Ute M Moll Frank Madeo Patrizia Paterlini-Brechot Rosario Rizzuto Gyorgy Szabadkai Gérard Pierron Klas Blomgren Nektarios Tavernarakis Patrice Codogno Francesco Cecconi Guido Kroemer doi:10.1038/ncb1730 Nature cell biology (4 May 2008) 2008-05-09T20:16:01-00:00 2008 Nature cell biology 1465-7392 autophagy