Article

Autophagy and signaling: Their role in cell survival and cell death

University of Amsterdam, Amsterdamo, North Holland, Netherlands
Cell Death and Differentiation (Impact Factor: 8.18). 12/2005; 12 Suppl 2(Suppl 2):1509-18. DOI: 10.1038/sj.cdd.4401751
Source: PubMed

ABSTRACT

Macroautophagy is a vacuolar, self-digesting mechanism responsible for the removal of long-lived proteins and damaged organelles by the lysosome. The discovery of the ATG genes has provided key information about the formation of the autophagosome, and about the role of macroautophagy in allowing cells to survive during nutrient depletion and/or in the absence of growth factors. Two connected signaling pathways encompassing class-I phosphatidylinositol 3-kinase and (mammalian) target of rapamycin play a central role in controlling macroautophagy in response to starvation. However, a considerable body of literature reports that macroautophagy is also a cell death mechanism that can occur either in the absence of detectable signs of apoptosis (via autophagic cell death) or concomitantly with apoptosis. Macroautophagy is activated by signaling pathways that also control apoptosis. The aim of this review is to discuss the signaling pathways that control macroautophagy during cell survival and cell death.

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Available from: Alfred J Meijer
    • "More recent studies suggest the role of miR-199a-5p in autophagic regulation following irradiation[52]. Interestingly, autophagy has been reported to control miRNA biogenesis and activity, suggesting a feedback loop between miRNAs and autophagy[53]. Over expression of this miRNA has been shown to suppress radiation-induced autophagy in MCF7 breast cancer cell line[54,55]. "
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    ABSTRACT: Autophagy is an evolutionary conserved, indispensable, lysosome-mediated degradation process, which helps in maintaining homeostasis during various cellular traumas. During stress, a context-dependent role of autophagy has been observed which drives the cell towards survival or death depending upon the type, time, and extent of the damage. The process of autophagy is stimulated during various cellular insults, e.g. oxidative stress, endoplasmic reticulum stress, imbalances in calcium homeostasis, and altered mitochondrial potential. Ionizing radiation causes ROS-dependent as well as ROS-independent damage in cells that involve macromolecular (mainly DNA) damage, as well as ER stress induction, both capable of inducing autophagy. This review summarizes the current understanding on the roles of oxidative stress, ER stress, DNA damage, altered mitochondrial potential, and calcium imbalance in radiation-induced autophagy as well as the merits and limitations of targeting autophagy as an approach for radioprotection and radiosensitization.
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    • "The autophagy signaling, which constitutes the second pathway, is important for maintain‐ ing cell metabolism and organelle turnover. It involves the degradation of substrates by hydrolases into a vesicle called lysosome [18]. Recent evidence demonstrates cross talk and cooperation between the ubiquitin-proteasome system and autophagy [19] [20]. "
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    ABSTRACT: Autophagy is an evolutionarily conserved intracellular system that selectively eliminates protein aggregates, damaged organelles, and other cellular debris. It is a self-cleaning process critical for cell homeostasis in conditions of energy stress. Autophagy has been until now relatively overlooked in skeletal muscle, but recent data highlight its vital role in this tissue in response to several stress conditions. The most recognized sensors for autophagy modulation are the adenosine monophosphate (AMP)-activated protein kinase (AMPK) and the mechanistic target of rapamycin (MTOR). AMPK acts as a sensor of cellular energy status by regulating several intracellular systems including glucose and lipid metabolisms and mitochondrial biogenesis. Recently, AMPK has been involved in the control of protein synthesis by decreasing MTOR activity and in the control of protein breakdown programs. Concerning proteolysis, AMPK notably regulates autophagy through FoxO transcription factors and Ulk1 complex. In this chapter, we describe the functioning of the different autophagy pathways (macroautophagy, microautophagy, and chaperone-mediated autophagy) in skeletal muscle and define the role of macroautophagy in response to physical exercise, a stress that is well assumed to be a key strategy to counteract metabolic and muscle diseases. The effects of dietary factors and altitude exposure are also discussed in the context of exercise.
    Full-text · Chapter · Sep 2015
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    • "Upon autophagy induction, a double membrane, called isolation membrane, surrounds material to be degraded and forms an autophagosome. It grows and moves along microtubules and finally fuses with lysosomes, where the sequestered material is hydrolyzed to amino acids and other simple compounds that can be reused by the cell (Codogno and Meijer, 2005; Levine and Klionsky, 2004; Meijer and Codogno, 2009). At the molecular level this process is driven by products of autophagy-related genes (ATG) which are necessary for each step of autophagy (Noda et al., 2002). "
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    ABSTRACT: It is well established that mTORC1 suppresses autophagy by phosphorylation and inactivation of proteins involved in autophagosome formation. However, the role of its substrate, p70S6 kinase1 (S6K1), in autophagy is quite controversial. In some models S6K1 activity correlates with autophagy suppression, however, some other studies show that S6K1 promotes rather than inhibits this process. Here, we investigated the role of S6K1 in prostate cancer cells (PC-3) and non-cancerous, mouse embryonic fibroblasts (MEF), either treated with autophagy inducer sulforaphane, an isothiocyanate derived from cruciferous plants, or deprived of serum. Our results indicate that constitutively active S6K1 decreases the level of LC3 processing and foci formation by autophagosomal vacuoles in cells treated with sulforaphane. On the other hand, presence of S6K1 is necessary for autophagosome maturation under conditions of autophagy induced by either sulforaphane or serum deprivation. Diminished level of S6K1 or lack of S6 kinases results in both, accumulation of autophagosomes and drop in the autophagolysosome number, and thus disturbs autophagy flux under stress conditions. Moreover, lack of S6 kinases reduces cell survival under stress conditions. Copyright © 2015 Elsevier GmbH. All rights reserved.
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