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Mizushima NAutophagy: process and function. Genes Dev 21:2861-2873

Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113-8519, Japan.
Genes & Development (Impact Factor: 12.64). 12/2007; 21(22):2861-73. DOI: 10.1101/gad.1599207
Source: PubMed

ABSTRACT Autophagy is an intracellular degradation system that delivers cytoplasmic constituents to the lysosome. Despite its simplicity, recent progress has demonstrated that autophagy plays a wide variety of physiological and pathophysiological roles, which are sometimes complex. Autophagy consists of several sequential steps--sequestration, transport to lysosomes, degradation, and utilization of degradation products--and each step may exert different function. In this review, the process of autophagy is summarized, and the role of autophagy is discussed in a process-based manner.

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    • "the cells (Meijer et al 2004; Gozuacik et al 2007; Mizushima et al 2007; Baehrecke et al 2005). Based on these findings, we hypothesize that Vitamin C reduces oxidative stress and regulates autophagy and apoptosis in BMSCs through the SVCT2 transporter. "
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    ABSTRACT: Vitamin C is an antioxidant that plays a vital role in various biological processes including bone formation. Previously, we reported that vitamin C is transported into bone marrow stromal cells (BMSCs) through the sodium dependent Vitamin C Transporter 2 (SVCT2) and this transporter plays an important role in osteogenic differentiation. Furthermore, this transporter is regulated by oxidative stress. To date, however, the exact role of vitamin C and its transporter (SVCT2) in ROS regulated autophagy and apoptosis in BMSCs is poorly understood. In the present study, we observed that oxidative stress decreased survival of BMSCs in a dose-dependent manner and induced growth arrest in the G1 phase of the cell cycle. These effects were accompanied by the induction of autophagy, confirmed by P62 and LC3B protein level and punctate GFP-LC3B distribution. The supplementation of vitamin C significantly rescued the BMSCs from oxidative stress by regulating autophagy. Knockdown of the SVCT2 transporter in BMSCs synergistically decreased cell survival even under low oxidative stress conditions. Also, supplementing vitamin C failed to rescue cells from stress. Our results reveal that the SVCT2 transporter plays a vital role in the mechanism of BMSC survival under stress conditions. Altogether, this study has given new insight into the role of the SVCT2 transporter in oxidative stress related autophagy and apoptosis in BMSCs. Published by Elsevier B.V.
    Stem Cell Research 06/2015; 6(2). DOI:10.1016/j.scr.2015.06.002 · 3.91 Impact Factor
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    • "In eukaryotes, there are two main degradation systems for cytoplasmic proteins, that is, the ubiquitin-proteasome system (UPS) and autophagy. The UPS is mainly involved in selective clearance for short-lived proteins [13], while autophagy is the mechanism by which the long-lived as well as misfolded proteins can be removed by the endolysosomal system [14] [15]. It is also noted that the involvement of endocytosis and vesicle trafficking in the regulation of protein homeostasis and degradation have recently emerged [10, 16–18]. "
    Dataset: ALS 2012NRI
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    • "Altered expression of the clock genes has been evidenced in pancreatic malignant neoplasms as well (Pogue-Geile et al., 2006; Relles et al., 2013). In this regard, PC is characterized by elevated levels of autophagy , a catabolic process that manages the lysosomal degradation of waste or altered molecules and cellular organelles with the aim to recycle bioenergetic components (Mizushima, 2007). In the context of pancreatic malignant neoplasms, activated autophagy supports tumor growth and plays a role in lack of effect of actual treatments (Yang et al., 2011). "
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    ABSTRACT: Pancreatic cancer (PC), the fourth leading cause of cancer-related deaths, is characterized by high aggressiveness and resistance to chemotherapy. Pancreatic carcinogenesis is kept going by derangement of essential cell processes, such as proliferation, apoptosis, metabolism and autophagy, characterized by rhythmic variations with 24-h periodicity driven by the biological clock. We assessed the expression of the circadian genes ARNLT, ARNLT2, CLOCK, PER1, PER2, PER3, CRY1, CRY2 and the starvation-activated histone/protein deacetylase SIRT1 in 34 matched tumor and non-tumor tissue specimens of PC patients, and evaluated in PC derived cell lines if the modulation of SIRT1 expression through starvation could influence the temporal pattern of expression of the circadian genes. We found a significant down-regulation of ARNLT (p = 0.015), CRY1 (p = 0.013), CRY2 (p = 0.001), PER1 (p < 0.0001), PER2 (p < 0.001), PER3 (p = 0.001) and SIRT1 (p = 0.017) in PC specimens. PER3 and CRY2 expression levels were lower in patients with jaundice at diagnosis ( < 0.05). Having adjusted for age, adjuvant therapy and tumor stage, we evidenced that patients with higher PER2 and lower SIRT1 expression levels showed lower mortality (p = 0.028). Levels and temporal patterns of expression of many circadian genes and SIRT1 significantly changed upon serum starvation in vitro, with differences among four different PC cell lines examined (BXPC3, CFPAC, MIA-PaCa-2 and PANC-1). Serum deprivation induced changes of the overall mean level of the wave and amplitude, lengthened or shortened the cycle time and phase-advanced or phase-delayed the rhythmic oscillation depending on the gene and the PC cell line examined. In conclusion, a severe deregulation of expression of SIRT1 and circadian genes was evidenced in the cancer specimens of PC patients, and starvation influenced gene expression in PC cell lines, suggesting that the altered interplay between SIRT1 and the core circadian proteins could represent a crucial player in the process of pancreatic carcinogenesis.
    Chronobiology International 03/2015; 32(4):1-16. DOI:10.3109/07420528.2014.1003351 · 2.88 Impact Factor
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