International Journal of Cell Biology最新文献

{"title":"Selective Activation of Cancer Stem Cells by Size-Specific Hyaluronan in Head and Neck Cancer.","authors":"Marisa Shiina,&nbsp;Lilly Y W Bourguignon","doi":"10.1155/2015/989070","DOIUrl":"https://doi.org/10.1155/2015/989070","url":null,"abstract":"<p><p>We determined that human head and neck cancer cells (HSC-3 cell line) contain a subpopulation displaying cancer stem cell (CSC) properties and are very tumorigenic. Specifically, we investigated whether different sizes of hyaluronan (HA) (e.g., 5 kDa, 20 kDa, 200 kDa, or 700 kDa-HA-sizes) play a role in regulating these CSCs. First, we observed that 200 kDa-HA (but not other sizes of HA) preferentially induces certain stem cell marker expression resulting in self-renewal and clonal formation of these cells. Further analyses indicate that 200 kDa-HA selectively stimulates the expression of a panel of microRNAs (most noticeably miR-10b) in these CSCs. Survival protein (cIAP-1) expression was also stimulated by 200 kDa-HA in these CSCs leading to cisplatin resistance. Furthermore, our results indicate that the anti-miR-10 inhibitor not only decreases survival protein expression, but also increases chemosensitivity of the 200 kDa-HA-treated CSCs. These findings strongly support the contention that 200 kDa-HA plays a pivotal role in miR-10 production leading to survival protein upregulation and chemoresistance in CSCs. Together, our findings suggest that selective activation of oncogenic signaling by certain sizes of HA (e.g., 200 kDa-HA) may be instrumental in the formation of CSC functions leading to tumor cell survival and chemoresistance in head and neck cancer progression. </p>","PeriodicalId":39084,"journal":{"name":"International Journal of Cell Biology","volume":"2015 ","pages":"989070"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2015/989070","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34138716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intermittent Compressive Stress Enhanced Insulin-Like Growth Factor-1 Expression in Human Periodontal Ligament Cells.","authors":"Jittima Pumklin,&nbsp;Jeeranan Manokawinchoke,&nbsp;Kanokporn Bhalang,&nbsp;Prasit Pavasant","doi":"10.1155/2015/369874","DOIUrl":"https://doi.org/10.1155/2015/369874","url":null,"abstract":"<p><p>Mechanical force was shown to promote IGF-1 expression in periodontal ligament both in vitro and in vivo. Though the mechanism of this effect has not yet been proved, here we investigated the molecular mechanism of intermittent mechanical stress on IGF-1 expression. In addition, the role of hypoxia on the intermittent compressive stress on IGF-1 expression was also examined. In this study, human periodontal ligament cells (HPDLs) were stimulated with intermittent mechanical stress for 24 hours. IGF-1 expression was examined by real-time polymerase chain reaction. Chemical inhibitors were used to determine molecular mechanisms of these effects. For hypoxic mimic condition, the CoCl2 supplementation was employed. The results showed that intermittent mechanical stress dramatically increased IGF-1 expression at 24 h. The pretreatment with TGF-β receptor I or TGF-β1 antibody could inhibit the intermittent mechanical stress-induced IGF-1 expression. Moreover, the upregulation of TGF-β1 proteins was detected in intermittent mechanical stress treated group. Correspondingly, the IGF-1 expression was upregulated upon being treated with recombinant human TGF-β1. Further, the hypoxic mimic condition attenuated the intermittent mechanical stress and rhTGF-β1-induced IGF-1 expression. In summary, this study suggests intermittent mechanical stress-induced IGF-1 expression in HPDLs through TGF-β1 and this phenomenon could be inhibited in hypoxic mimic condition. </p>","PeriodicalId":39084,"journal":{"name":"International Journal of Cell Biology","volume":"2015 ","pages":"369874"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2015/369874","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33413967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell biology of cysteine-based molecular switches.","authors":"Christian Appenzeller-Herzog,&nbsp;Kenji Inaba,&nbsp;Agnès Delaunay-Moisan","doi":"10.1155/2014/157038","DOIUrl":"https://doi.org/10.1155/2014/157038","url":null,"abstract":"Reversible posttranslational protein modifications form the mechanistic basis for the reception and propagation of biological signals in cells. Besides other modifications such as phosphorylation, acetylation, ADP-ribosylation, and ubiquitylation, reduction-oxidation (redox) processes allow reversible structure-function modulation of proteins, which serve as molecular on-off switches in cell biology. Although many protein-bound amino acids and even the peptide backbone can react with oxidizing metabolites during oxidative stress, only three amino acids adopt reversible redox modifications: cysteine, selenocysteine, and methionine. Among these, cysteine-based molecular switches are by far the most prevalent and best studied. Cysteine switches (or “sulfur switches”) respond in heterogeneous, context-dependent manner to a variety of stimuli (endogenous metabolites, chemicals from the diet, xenobiotics, or air oxidants) by direct modification. Common covalent modifications of cysteines include intra- or intermolecular protein-protein disulfide-bond formation, S-glutathionylation, S-cysteinylation, S-nitrosylation, sulfoxidation, and sulfhydration. \u0000 \u0000Catalyzed, redox-dependent on-off cycles of cysteine centers in proteins regulate processes as diverse as protein folding, aggregation, and trafficking, enzymatic activity, metal chelation, DNA, RNA, protein, or membrane binding, and channel opening. In this special issue, we have attempted to illustrate the versatility of cysteine-based protein regulation and its impact on the physiology of cells and organisms. \u0000 \u0000In both the secretory pathway and the mitochondrial intermembrane space (IMS), protein maturation often requires the introduction of disulfide crosslinks to promote or maintain protein structure. During this process known as oxidative protein folding, introduced disulfide bridges can be reshuffled, until the native conformation is achieved. Dedicated oxidative folding catalysts, as reviewed by Y. Onda, exist in the endoplasmic reticulum (ER), IMS, and chloroplasts in plant cells as well as in the extracellular space. The disulfide-generating machineries in ER and IMS are conserved in plants, fungi, and animals. Evolutionary and mechanistic aspects of disulfide-bond formation in IMS are discussed by M. Fischer and J. Riemer. Interestingly, the core components of this machinery, Erv1/ALR and Mia40, have additional, poorly understood functions in liver regeneration and hypoxia response, which are likely fulfilled through mechanisms other than oxidative folding in IMS. \u0000 \u0000Two contributions are concerned with the involvement of cysteines in the regulation of antibody secretion and differentiation of B lymphocytes. The review article by T. Anelli and E. van Anken enlightens how cysteine redox status acts as a quality control checkpoint to ensure that only mature IgM antibodies leave the compartments of the early secretory pathway en route to the blood stream. Immature antibodies are tagged with a fr","PeriodicalId":39084,"journal":{"name":"International Journal of Cell Biology","volume":"2014 ","pages":"157038"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/157038","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32191232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Necrostatin-1 reduces neurovascular injury after intracerebral hemorrhage.","authors":"Melanie D King,&nbsp;Wittstatt A Whitaker-Lea,&nbsp;James M Campbell,&nbsp;Cargill H Alleyne,&nbsp;Krishnan M Dhandapani","doi":"10.1155/2014/495817","DOIUrl":"https://doi.org/10.1155/2014/495817","url":null,"abstract":"<p><p>Intracerebral hemorrhage (ICH) is the most common form of hemorrhagic stroke, accounting for 15% of all strokes. ICH has the highest acute mortality and the worst long-term prognosis of all stroke subtypes. Unfortunately, the dearth of clinically effective treatment options makes ICH the least treatable form of stroke, emphasizing the need for novel therapeutic targets. Recent work by our laboratory identified a novel role for the necroptosis inhibitor, necrostatin-1, in limiting neurovascular injury in tissue culture models of hemorrhagic injury. In the present study, we tested the hypothesis that necrostatin-1 reduces neurovascular injury after collagenase-induced ICH in mice. Necrostatin-1 significantly reduced hematoma volume by 54% at 72 h after-ICH, as compared to either sham-injured mice or mice administered an inactive, structural analogue of necrostatin-1. Necrostatin-1 also limited cell death by 48%, reduced blood-brain barrier opening by 51%, attenuated edema development to sham levels, and improved neurobehavioral outcomes after ICH. These data suggest a potential clinical utility for necrostatin-1 and/or novel necroptosis inhibitors as an adjunct therapy to reduce neurological injury and improve patient outcomes after ICH. </p>","PeriodicalId":39084,"journal":{"name":"International Journal of Cell Biology","volume":"2014 ","pages":"495817"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/495817","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32261092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protein misfolding and neurodegenerative diseases.","authors":"Alessio Cardinale,&nbsp;Roberto Chiesa,&nbsp;Michael Sierks","doi":"10.1155/2014/217371","DOIUrl":"https://doi.org/10.1155/2014/217371","url":null,"abstract":"This special issue includes fifteen reviews and two original research articles by leading scientists in the fields of neuropathology, biochemistry, and cell biology, dealing with the role of protein aggregation and prion-like propagation of protein misfolding in neurodegenerative diseases. \u0000 \u0000In the review article “Breaking the code of amyloid-β oligomers,” available at the following link: http://www.hindawi.com/journals/ijcb/2013/950783/, S. E. Lesne outlines the “oligomeric” view of the amyloid hypothesis in Alzheimer's disease (AD), discussing how structurally different amyloid-β (Aβ) oligomers may contribute to the pathogenesis, and the controversial role of the prion protein (PrP) in Aβ toxicity. He stresses the need to thoroughly characterize the oligomeric Aβ assemblies for dissecting the disease mechanisms and designing specific, effective therapies. \u0000 \u0000Tau oligomers may also play an important neurotoxic role in AD. In the research article “Trimeric tau is toxic to human neuronal cells at low nanomolar concentrations,” available at the following link: http://www.hindawi.com/journals/ijcb/2013/260787/, H. Tian et al. show that two nonphosphorylated human recombinant tau splice variants are neurotoxic at low nanomolar concentrations. They provide evidence that trimeric but not monomeric or dimeric tau is responsible for the toxicity. In the review article “The innate immune system in Alzheimer's disease,” available at the following link: http://www.hindawi.com/journals/ijcb/2013/576383/, A. Boutajangout and T. Wisniewski focus on the potential roles of the triggering receptor expressed on myeloid cells 2 protein (TREM2) and Toll-like receptors (TLRs) in AD. They give an overview of TREM2 functions and its involvement in phagocytic and anti-inflammatory pathways. They also review the critical roles of TLR4 and 9 in the innate immune response, the interplay of these pattern recognition receptors, and highlight the importance of microglia-mediated innate immunity in AD pathogenesis. \u0000 \u0000Several articles deal with the cellular processes involved in protein folding and quality control and how their corruption may trigger neurotoxicity. In the review article “Disulfide bonding in neurodegenerative misfolding diseases,” available at the following link: http://www.hindawi.com/journals/ijcb/2013/318319/, M. F. Mossuto discusses the role of disulfide bond formation; in the review article “Role of protein misfolding and proteostasis deficiency in protein misfolding diseases and aging,” available at the following link: http://www.hindawi.com/journals/ijcb/2013/638083/, K. Cuanalo-Contreras et al. review the involvement of the unfolded protein response (UPR), the ubiquitin proteasome system (UPS), autophagy, and aggresome formation in neurodegenerative diseases and aging. In the review article “ER dysfunction and protein folding stress in ALS,” available at the following link: http://www.hindawi.com/journals/ijcb/2013/674751/, S. Matus et al. specificall","PeriodicalId":39084,"journal":{"name":"International Journal of Cell Biology","volume":"2014 ","pages":"217371"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/217371","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32317208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"S-nitrosation and ubiquitin-proteasome system interplay in neuromuscular disorders.","authors":"Salvatore Rizza,&nbsp;Costanza Montagna,&nbsp;Giuseppina Di Giacomo,&nbsp;Claudia Cirotti,&nbsp;Giuseppe Filomeni","doi":"10.1155/2014/428764","DOIUrl":"https://doi.org/10.1155/2014/428764","url":null,"abstract":"<p><p>Protein S-nitrosation is deemed as a prototype of posttranslational modifications governing cell signaling. It takes place on specific cysteine residues that covalently incorporate a nitric oxide (NO) moiety to form S-nitrosothiol derivatives and depends on the ratio between NO produced by NO synthases and nitrosothiol removal catalyzed by denitrosating enzymes. A large number of cysteine-containing proteins are found to undergo S-nitrosation and, among them, the enzymes catalyzing ubiquitination, mainly the class of ubiquitin E3 ligases and the 20S component of the proteasome, have been reported to be redox modulated in their activity. In this review we will outline the processes regulating S-nitrosation and try to debate whether and how it affects protein ubiquitination and degradation via the proteasome. In particular, since muscle and neuronal health largely depends on the balance between protein synthesis and breakdown, here we will discuss the impact of S-nitrosation in the efficiency of protein quality control system, providing lines of evidence and speculating about its involvement in the onset and maintenance of neuromuscular dysfunctions. </p>","PeriodicalId":39084,"journal":{"name":"International Journal of Cell Biology","volume":"2014 ","pages":"428764"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/428764","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32174100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"2-cys peroxiredoxins: emerging hubs determining redox dependency of Mammalian signaling networks.","authors":"Jinah Park,&nbsp;Sunmi Lee,&nbsp;Sanghyuk Lee,&nbsp;Sang Won Kang","doi":"10.1155/2014/715867","DOIUrl":"https://doi.org/10.1155/2014/715867","url":null,"abstract":"<p><p>Mammalian cells have a well-defined set of antioxidant enzymes, which includes superoxide dismutases, catalase, glutathione peroxidases, and peroxiredoxins. Peroxiredoxins are the most recently identified family of antioxidant enzymes that catalyze the reduction reaction of peroxides, such as H2O2. In particular, typical 2-Cys peroxiredoxins are the featured peroxidase enzymes that receive the electrons from NADPH by coupling with thioredoxin and thioredoxin reductase. These enzymes distribute throughout the cellular compartments and, therefore, are thought to be broad-range antioxidant defenders. However, recent evidence demonstrates that typical 2-Cys peroxiredoxins play key signal regulatory roles in the various signaling networks by interacting with or residing near a specific redox-sensitive molecule. These discoveries help reveal the redox signaling landscape in mammalian cells and may further provide a new paradigm of therapeutic approaches based on redox signaling. </p>","PeriodicalId":39084,"journal":{"name":"International Journal of Cell Biology","volume":"2014 ","pages":"715867"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/715867","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32212719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of autophagy on cell death modalities.","authors":"Stefan W Ryter, Kenji Mizumura, Augustine M K Choi","doi":"10.1155/2014/502676","DOIUrl":"10.1155/2014/502676","url":null,"abstract":"<p><p>Autophagy represents a homeostatic cellular mechanism for the turnover of organelles and proteins, through a lysosome-dependent degradation pathway. During starvation, autophagy facilitates cell survival through the recycling of metabolic precursors. Additionally, autophagy can modulate other vital processes such as programmed cell death (e.g., apoptosis), inflammation, and adaptive immune mechanisms and thereby influence disease pathogenesis. Selective pathways can target distinct cargoes (e.g., mitochondria and proteins) for autophagic degradation. At present, the causal relationship between autophagy and various forms of regulated or nonregulated cell death remains unclear. Autophagy can occur in association with necrosis-like cell death triggered by caspase inhibition. Autophagy and apoptosis have been shown to be coincident or antagonistic, depending on experimental context, and share cross-talk between signal transduction elements. Autophagy may modulate the outcome of other regulated forms of cell death such as necroptosis. Recent advances suggest that autophagy can dampen inflammatory responses, including inflammasome-dependent caspase-1 activation and maturation of proinflammatory cytokines. Autophagy may also act as regulator of caspase-1 dependent cell death (pyroptosis). Strategies aimed at modulating autophagy may lead to therapeutic interventions for diseases in which apoptosis or other forms of regulated cell death may play a cardinal role. </p>","PeriodicalId":39084,"journal":{"name":"International Journal of Cell Biology","volume":"2014 ","pages":"502676"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3932252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32184243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial DNA and functional investigations into the radiosensitivity of four mouse strains.","authors":"Steven B Zhang, David Maguire, Mei Zhang, Yeping Tian, Shanmin Yang, Amy Zhang, Katherine Casey-Sawicki, Deping Han, Jun Ma, Liangjie Yin, Yongson Guo, Xiaohui Wang, Chun Chen, Alexandra Litvinchuk, Zhenhuan Zhang, Steven Swarts, Sadasivan Vidyasagar, Lurong Zhang, Paul Okunieff","doi":"10.1155/2014/850460","DOIUrl":"10.1155/2014/850460","url":null,"abstract":"<p><p>We investigated whether genetic radiosensitivity-related changes in mtDNA/nDNA ratios are significant to mitochondrial function and if a material effect on mtDNA content and function exists. BALB/c (radiosensitive), C57BL/6 (radioresistant), and F1 hybrid mouse strains were exposed to total body irradiation. Hepatic genomic DNA was extracted, and mitochondria were isolated. Mitochondrial oxygen consumption, ROS, and calcium-induced mitochondrial swelling were measured. Radiation influenced strain-specific survival in vivo. F1 hybrid survival was influenced by maternal input. Changes in mitochondrial content corresponded to survival in vivo among the 4 strains. Calcium-induced mitochondrial swelling was strain dependent. Isolated mitochondria from BALB/c mice were significantly more sensitive to calcium overload than mitochondria from C57BL/6 mice. Maternal input partially influenced the recovery effect of radiation on calcium-induced mitochondrial swelling in F1 hybrids; the hybrid with a radiosensitive maternal lineage exhibited a lower rate of recovery. Hybrids had a survival rate that was biased toward maternal input. mtDNA content and mitochondrial permeability transition pores (MPTP) measured in these strains before irradiation reflected a dominant input from the parent. After irradiation, the MPTP opened sooner in radiosensitive and hybrid strains, likely triggering intrinsic apoptotic pathways. These findings have important implications for translation into predictors of radiation sensitivity/resistance. </p>","PeriodicalId":39084,"journal":{"name":"International Journal of Cell Biology","volume":"2014 ","pages":"850460"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3944901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32223795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Linking Peroxiredoxin and Vacuolar-ATPase Functions in Calorie Restriction-Mediated Life Span Extension.","authors":"Mikael Molin, Ayse Banu Demir","doi":"10.1155/2014/913071","DOIUrl":"10.1155/2014/913071","url":null,"abstract":"<p><p>Calorie restriction (CR) is an intervention extending the life spans of many organisms. The mechanisms underlying CR-dependent retardation of aging are still poorly understood. Despite mechanisms involving conserved nutrient signaling pathways proposed, few target processes that can account for CR-mediated longevity have so far been identified. Recently, both peroxiredoxins and vacuolar-ATPases were reported to control CR-mediated retardation of aging downstream of conserved nutrient signaling pathways. In this review, we focus on peroxiredoxin-mediated stress-defence and vacuolar-ATPase regulated acidification and pinpoint common denominators between the two mechanisms proposed for how CR extends life span. Both the activities of peroxiredoxins and vacuolar-ATPases are stimulated upon CR through reduced activities in conserved nutrient signaling pathways and both seem to stimulate cellular resistance to peroxide-stress. However, whereas vacuolar-ATPases have recently been suggested to control both Ras-cAMP-PKA- and TORC1-mediated nutrient signaling, neither the physiological benefits of a proposed role for peroxiredoxins in H2O2-signaling nor downstream targets regulated are known. Both peroxiredoxins and vacuolar-ATPases do, however, impinge on mitochondrial iron-metabolism and further characterization of their impact on iron homeostasis and peroxide-resistance might therefore increase our understanding of the beneficial effects of CR on aging and age-related diseases. </p>","PeriodicalId":39084,"journal":{"name":"International Journal of Cell Biology","volume":"2014 ","pages":"913071"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3930189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32184246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}