#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#
preLekára.sk / Odborné časopisy / PLOS Genetics / 2015 - 2

Mitochondrial and Cytoplasmic ROS Have Opposing Effects on Lifespan

English version České info

The accumulation of oxidative damage caused by reactive oxygen species (ROS) has been proposed to be one of the main causes of aging. However, recent work indicates that low levels of ROS can be beneficial and promote longevity. In this paper, we use a long-lived mitochondrial mutant C. elegans strain clk-1 to further examine the relationship between ROS and lifespan. While it was originally believed that clk-1 mutants had increased lifespan as a result of decreased ROS production, ROS levels have been shown to be increased in clk-1 worms. We show that this increase in ROS is required for the longevity of clk-1 worms as treatment with antioxidants decreases clk-1 lifespan. Further, by using a genetic approach to increase ROS in specific subcellular compartments, we show that the location of the ROS is crucial in determining its effect on lifespan. Increasing ROS in the mitochondria markedly increases clk-1 lifespan, while increasing ROS in the cytoplasm decreases it. Finally, we show that the effect of increased ROS on stress resistance and physiologic rates is also dependent on the location of ROS within the cell but that both of these factors can be experimentally dissociated from lifespan.

Vyšlo v časopise: Mitochondrial and Cytoplasmic ROS Have Opposing Effects on Lifespan. PLoS Genet 11(2): e32767. doi:10.1371/journal.pgen.1004972
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004972

Souhrn

The accumulation of oxidative damage caused by reactive oxygen species (ROS) has been proposed to be one of the main causes of aging. However, recent work indicates that low levels of ROS can be beneficial and promote longevity. In this paper, we use a long-lived mitochondrial mutant C. elegans strain clk-1 to further examine the relationship between ROS and lifespan. While it was originally believed that clk-1 mutants had increased lifespan as a result of decreased ROS production, ROS levels have been shown to be increased in clk-1 worms. We show that this increase in ROS is required for the longevity of clk-1 worms as treatment with antioxidants decreases clk-1 lifespan. Further, by using a genetic approach to increase ROS in specific subcellular compartments, we show that the location of the ROS is crucial in determining its effect on lifespan. Increasing ROS in the mitochondria markedly increases clk-1 lifespan, while increasing ROS in the cytoplasm decreases it. Finally, we show that the effect of increased ROS on stress resistance and physiologic rates is also dependent on the location of ROS within the cell but that both of these factors can be experimentally dissociated from lifespan.

Zdroje

1. Harman D (1956) Aging: a theory based on free radical and radiation chemistry. JGerontol 11 : 298–300. 13332224

2. D'Autreaux B, Toledano MB (2007) ROS as signalling molecules: mechanisms that generate specificity in ROS homeostasis. NatRevMolCell Biol 8 : 813–824.

3. Yang W, Hekimi S (2010) A mitochondrial superoxide signal triggers increased longevity in Caenorhabditis elegans. PLoS Biol 8: e1000556. doi: 10.1371/journal.pbio.1000556 21151885

4. Van Raamsdonk JM, Hekimi S (2012) Superoxide dismutase is dispensable for normal animal lifespan. Proc Natl Acad Sci U S A 109 : 5785–5790. doi: 10.1073/pnas.1116158109 22451939

5. Lee SJ, Hwang AB, Kenyon C (2010) Inhibition of respiration extends C. elegans life span via reactive oxygen species that increase HIF-1 activity. Curr Biol 20 : 2131–2136. doi: 10.1016/j.cub.2010.10.057 21093262

6. Shibata Y, Branicky R, Landaverde IO, Hekimi S (2003) Redox regulation of germline and vulval development in Caenorhabditis elegans. Science 302 : 1779–1782. 14657502

7. Van Raamsdonk JM, Hekimi S (2009) Deletion of the mitochondrial superoxide dismutase sod-2 extends lifespan in Caenorhabditis elegans. PLoS Genet 5: e1000361. doi: 10.1371/journal.pgen.1000361 19197346

8. Zarse K, Schmeisser S, Groth M, Priebe S, Beuster G, et al. (2012) Impaired insulin/IGF1 signaling extends life span by promoting mitochondrial L-proline catabolism to induce a transient ROS signal. Cell metabolism 15 : 451–465. doi: 10.1016/j.cmet.2012.02.013 22482728

9. Wong A, Boutis P, Hekimi S (1995) Mutations in the clk-1 gene of Caenorhabditis elegans affect developmental and behavioral timing. Genetics 139 : 1247–1259. 7768437

10. Lakowski B, Hekimi S (1996) Determination of life-span in Caenorhabditis elegans by four clock genes. Science 272 : 1010–1013. 8638122

11. Ewbank JJ, Barnes TM, Lakowski B, Lussier M, Bussey H, et al. (1997) Structural and functional conservation of the Caenorhabditis elegans timing gene clk-1. Science 275 : 980–983. 9020081

12. Stepanyan Z, Hughes B, Cliche DO, Camp D, Hekimi S (2006) Genetic and molecular characterization of CLK-1/mCLK1, a conserved determinant of the rate of aging. ExpGerontol.

13. Braeckman BP, Houthoofd K, De Vreese A, Vanfleteren JR (1999) Apparent uncoupling of energy production and consumption in long-lived Clk mutants of Caenorhabditis elegans. Curr Biol 9 : 493–496. 10330373

14. Yang W, Li J, Hekimi S (2007) A Measurable increase in oxidative damage due to reduction in superoxide detoxification fails to shorten the life span of long-lived mitochondrial mutants of Caenorhabditis elegans. Genetics 177 : 2063–2074. 18073424

15. Van Raamsdonk JM, Meng Y, Camp D, Yang W, Jia X, et al. (2010) Decreased energy metabolism extends life span in Caenorhabditis elegans without reducing oxidative damage. Genetics 185 : 559–571. doi: 10.1534/genetics.110.115378 20382831

16. Felkai S, Ewbank JJ, Lemieux J, Labbe JC, Brown GG, et al. (1999) CLK-1 controls respiration, behavior and aging in the nematode Caenorhabditis elegans. Embo J 18 : 1783–1792. 10202142

17. Kayser EB, Sedensky MM, Morgan PG, Hoppel CL (2004) Mitochondrial oxidative phosphorylation is defective in the long-lived mutant clk-1. JBiolChem 279 : 54479–54486. 15269213

18. Van Raamsdonk JM, Hekimi S (2010) Reactive Oxygen Species and Aging in Caenorhabditis elegans: Causal or Casual Relationship? Antioxid Redox Signal 13 : 1911–1953. doi: 10.1089/ars.2010.3215 20568954

19. Baker BM, Nargund AM, Sun T, Haynes CM (2012) Protective coupling of mitochondrial function and protein synthesis via the eIF2alpha kinase GCN-2. PLoS Genet 8: e1002760. doi: 10.1371/journal.pgen.1002760 22719267

20. Braeckman BP, Houthoofd K, Brys K, Lenaerts I, De Vreese A, et al. (2002) No reduction of energy metabolism in Clk mutants. Mech Ageing Dev 123 : 1447–1456. 12425951

21. Kayser EB, Sedensky MM, Morgan PG (2004) The effects of complex I function and oxidative damage on lifespan and anesthetic sensitivity in Caenorhabditis elegans. Mech Ageing Dev 125 : 455–464. 15178135

22. Yang YY, Gangoiti JA, Sedensky MM, Morgan PG (2009) The effect of different ubiquinones on lifespan in Caenorhabditis elegans. Mech Ageing Dev 130 : 370–376. doi: 10.1016/j.mad.2009.03.003 19428456

23. Labuschagne CF, Stigter EC, Hendriks MM, Berger R, Rokach J, et al. (2013) Quantification of in vivo oxidative damage in Caenorhabditis elegans during aging by endogenous F3-isoprostane measurement. Aging Cell 12 : 214–223. doi: 10.1111/acel.12043 23279719

24. Taub J, Lau JF, Ma C, Hahn JH, Hoque R, et al. (1999) A cytosolic catalase is needed to extend adult lifespan in C. elegans daf-C and clk-1 mutants. Nature 399 : 162–166. 10335847

25. Petriv OI, Rachubinski RA (2004) Lack of peroxisomal catalase causes a progeric phenotype in Caenorhabditis elegans. J Biol Chem 279 : 19996–20001. 14996832

26. Honda Y, Honda S (1999) The daf-2 gene network for longevity regulates oxidative stress resistance and Mn-superoxide dismutase gene expression in Caenorhabditis elegans. Faseb J 13 : 1385–1393. 10428762

27. Cristina D, Cary M, Lunceford A, Clarke C, Kenyon C (2009) A regulated response to impaired respiration slows behavioral rates and increases lifespan in Caenorhabditis elegans. PLoS Genet 5: e1000450. doi: 10.1371/journal.pgen.1000450 19360127

28. Jimenez-Hidalgo M, Kurz CL, Pedrajas JR, Naranjo-Galindo FJ, Gonzalez-Barrios M, et al. (2014) Functional characterization of thioredoxin 3 (TRX-3), a Caenorhabditis elegans intestine-specific thioredoxin. Free radical biology & medicine 68 : 205–219. doi: 10.1016/j.ejpn.2014.12.007 25553845

29. Leiers B, Kampkotter A, Grevelding CG, Link CD, Johnson TE, et al. (2003) A stress-responsive glutathione S-transferase confers resistance to oxidative stress in Caenorhabditis elegans. Free radical biology & medicine 34 : 1405–1415. doi: 10.1016/j.ejpn.2014.12.007 25553845

30. Yoneda T, Benedetti C, Urano F, Clark SG, Harding HP, et al. (2004) Compartment-specific perturbation of protein handling activates genes encoding mitochondrial chaperones. Journal of cell science 117 : 4055–4066. 15280428

31. Zhang Y, Shao Z, Zhai Z, Shen C, Powell-Coffman JA (2009) The HIF-1 hypoxia-inducible factor modulates lifespan in C. elegans. PloS one 4: e6348. doi: 10.1371/journal.pone.0006348 19633713

32. Landis GN, Tower J (2005) Superoxide dismutase evolution and life span regulation. MechAgeing Dev 126 : 365–379. 15664623

33. Giglio AM, Hunter T, Bannister JV, Bannister WH, Hunter GJ (1994) The copper/zinc superoxide dismutase gene of Caenorhabditis elegans. BiochemMolBiolInt 33 : 41–44.

34. Giglio MP, Hunter T, Bannister JV, Bannister WH, Hunter GJ (1994) The manganese superoxide dismutase gene of Caenorhabditis elegans. BiochemMolBiolInt 33 : 37–40.

35. Suzuki N, Inokuma K, Yasuda K, Ishii N (1996) Cloning, sequencing and mapping of a manganese superoxide dismutase gene of the nematode Caenorhabditis elegans. DNA Res 3 : 171–174. 8905235

36. Hunter T, Bannister WH, Hunter GJ (1997) Cloning, expression, and characterization of two manganese superoxide dismutases from Caenorhabditis elegans. JBiolChem 272 : 28652–28659. 9353332

37. Fujii M, Ishii N, Joguchi A, Yasuda K, Ayusawa D (1998) A novel superoxide dismutase gene encoding membrane-bound and extracellular isoforms by alternative splicing in Caenorhabditis elegans. DNA Res 5 : 25–30. 9628580

38. Jensen LT, Culotta VC (2005) Activation of CuZn superoxide dismutases from Caenorhabditis elegans does not require the copper chaperone CCS. JBiolChem 280 : 41373–41379. 16234242

39. Schulz TJ, Zarse K, Voigt A, Urban N, Birringer M, et al. (2007) Glucose restriction extends Caenorhabditis elegans life span by inducing mitochondrial respiration and increasing oxidative stress. Cell metabolism 6 : 280–293. 17908557

40. Schmeisser S, Zarse K, Ristow M (2011) Lonidamine extends lifespan of adult Caenorhabditis elegans by increasing the formation of mitochondrial reactive oxygen species. Hormone and metabolic research = Hormon -⁠ und Stoffwechselforschung = Hormones et metabolisme 43 : 687–692. doi: 10.1055/s-0031-1286308 21932172

41. Schmeisser S, Schmeisser K, Weimer S, Groth M, Priebe S, et al. (2013) Mitochondrial Hormesis Links Low-Dose Arsenite Exposure to Lifespan Extension. Aging cell doi: 10.1111/acel.12076 23534459

42. Schmeisser S, Priebe S, Groth M, Monajembashi S, Hemmerich P, et al. (2013) Neuronal ROS signaling rather than AMPK/sirtuin-mediated energy sensing links dietary restriction to lifespan extension. Mol Metab 2 : 92–102. doi: 10.1016/j.molmet.2013.02.002 24199155

43. Weimer S, Priebs J, Kuhlow D, Groth M, Priebe S, et al. (2014) D-Glucosamine supplementation extends life span of nematodes and of ageing mice. Nature communications 5 : 3563. doi: 10.1038/ncomms4563 24714520

44. Schmeisser K, Mansfeld J, Kuhlow D, Weimer S, Priebe S, et al. (2013) Role of sirtuins in lifespan regulation is linked to methylation of nicotinamide. Nature chemical biology doi: 10.1038/nchembio.1352 24077178

45. Feng J, Bussiere F, Hekimi S (2001) Mitochondrial electron transport is a key determinant of life span in Caenorhabditis elegans. Developmental cell 1 : 633–644. 11709184

46. Yang W, Hekimi S (2010) Two modes of mitochondrial dysfunction lead independently to lifespan extension in Caenorhabditis elegans. Aging cell 9 : 433–447. doi: 10.1111/j.1474-9726.2010.00571.x 20346072

47. Pan Y, Schroeder EA, Ocampo A, Barrientos A, Shadel GS (2011) Regulation of yeast chronological life span by TORC1 via adaptive mitochondrial ROS signaling. Cell metabolism 13 : 668–678. doi: 10.1016/j.cmet.2011.03.018 21641548

48. Liu X, Jiang N, Hughes B, Bigras E, Shoubridge E, et al. (2005) Evolutionary conservation of the clk-1-dependent mechanism of longevity: loss of mclk1 increases cellular fitness and lifespan in mice. Genes & development 19 : 2424–2434. doi: 10.1016/j.etap.2014.11.031 25555259

49. Gus'kova RA, Ivanov II, Kol'tover VK, Akhobadze VV, Rubin AB (1984) Permeability of bilayer lipid membranes for superoxide (O2-.) radicals. Biochim Biophys Acta 778 : 579–585. 6095912

50. Doonan R, McElwee JJ, Matthijssens F, Walker GA, Houthoofd K, et al. (2008) Against the oxidative damage theory of aging: superoxide dismutases protect against oxidative stress but have little or no effect on life span in Caenorhabditis elegans. Genes Dev 22 : 3236–3241. doi: 10.1101/gad.504808 19056880

51. Yen K, Mobbs CV (2010) Evidence for only two independent pathways for decreasing senescence in Caenorhabditis elegans. Age (Dordr) 32 : 39–49. doi: 10.1007/s11357-009-9110-7 19662517

52. Liu X, Jiang N, Hughes B, Bigras E, Shoubridge E, et al. (2005) Evolutionary conservation of the clk-1-dependent mechanism of longevity: loss of mclk1 increases cellular fitness and lifespan in mice. Genes Dev 19 : 2424–2434. 16195414

53. Lapointe J, Hekimi S (2008) Early Mitochondrial Dysfunction in Long-lived Mclk1+/ -⁠ Mice. JBiolChem 283 : 26217–26227. doi: 10.1074/jbc.M803287200 18635541

54. Braeckman BP, Houthoofd K, Brys K, Lenaerts I, De Vreese A, et al. (2002) No reduction of energy metabolism in Clk mutants. Mech Ageing Dev 123 : 1447–1456. 12425951

Štítky
Genetika Reprodukčná medicína
Článek 2014 Reviewer Thank You
Článek Systematic Cell-Based Phenotyping of Missense Alleles Empowers Rare Variant Association Studies: A Case for and Myocardial Infarction
Článek African Glucose-6-Phosphate Dehydrogenase Alleles Associated with Protection from Severe Malaria in Heterozygous Females in Tanzania
Článek Genomics of Divergence along a Continuum of Parapatric Population Differentiation
Článek microRNAs Regulate Cell-to-Cell Variability of Endogenous Target Gene Expression in Developing Mouse Thymocytes
Článek A Rolling Circle Replication Mechanism Produces Multimeric Lariats of Mitochondrial DNA in
Článek Closing the Gap between Knowledge and Clinical Application: Challenges for Genomic Translation
Článek Partially Redundant Enhancers Cooperatively Maintain Mammalian Expression Above a Critical Functional Threshold
Článek Discovery of Transcription Factors and Regulatory Regions Driving Tumor Development by ATAC-seq and FAIRE-seq Open Chromatin Profiling
Článek Mutations in Result in Ocular Coloboma, Microcornea and Cataracts
Článek A Genome-Wide Hybrid Incompatibility Landscape between and
Článek Recurrent Evolution of Melanism in South American Felids
Článek Discovery of CTCF-Sensitive Cis-Spliced Fusion RNAs between Adjacent Genes in Human Prostate Cells
Článek Tissue Expression Pattern of PMK-2 p38 MAPK Is Established by the miR-58 Family in
Článek Essential Role for Endogenous siRNAs during Meiosis in Mouse Oocytes
Článek Matrix Metalloproteinase 2 Is Required for Ovulation and Corpus Luteum Formation in
Článek Evolutionary Signatures amongst Disease Genes Permit Novel Methods for Gene Prioritization and Construction of Informative Gene-Based Networks
Článek RR-1 Cuticular Protein TcCPR4 Is Required for Formation of Pore Canals in Rigid Cuticle
Článek GC-Content Evolution in Bacterial Genomes: The Biased Gene Conversion Hypothesis Expands
Článek Proteotoxic Stress Induces Phosphorylation of p62/SQSTM1 by ULK1 to Regulate Selective Autophagic Clearance of Protein Aggregates
Článek K-homology Nuclear Ribonucleoproteins Regulate Floral Organ Identity and Determinacy in Arabidopsis
Článek A Nitric Oxide Regulated Small RNA Controls Expression of Genes Involved in Redox Homeostasis in
Článek HYPER RECOMBINATION1 of the THO/TREX Complex Plays a Role in Controlling Transcription of the Gene in Arabidopsis
Článek Structured Observations Reveal Slow HIV-1 CTL Escape
Článek An Integrative Multi-scale Analysis of the Dynamic DNA Methylation Landscape in Aging
Článek Combining Natural Sequence Variation with High Throughput Mutational Data to Reveal Protein Interaction Sites
Článek Transhydrogenase Promotes the Robustness and Evolvability of Deficient in NADPH Production
Článek Regulators of Autophagosome Formation in Muscles
Článek Genomic Selection and Association Mapping in Rice (): Effect of Trait Genetic Architecture, Training Population Composition, Marker Number and Statistical Model on Accuracy of Rice Genomic Selection in Elite, Tropical Rice Breeding Lines
Článek Eye Selector Logic for a Coordinated Cell Cycle Exit
Článek Inflammation-Induced Cell Proliferation Potentiates DNA Damage-Induced Mutations
Článek The DNA Polymerase δ Has a Role in the Deposition of Transcriptionally Active Epigenetic Marks, Development and Flowering
Článek Contribution of the Two Genes Encoding Histone Variant H3.3 to Viability and Fertility in Mice
Článek Membrane Recognition and Dynamics of the RNA Degradosome
Článek P-TEFb, the Super Elongation Complex and Mediator Regulate a Subset of Non-paused Genes during Early Embryo Development
Článek is a Long Non-coding RNA in JNK Signaling in Epithelial Shape Changes during Drosophila Dorsal Closure
Článek A Pleiotropy-Informed Bayesian False Discovery Rate Adapted to a Shared Control Design Finds New Disease Associations From GWAS Summary Statistics
Článek Genome-wide Association Study Identifies Shared Risk Loci Common to Two Malignancies in Golden Retrievers
Článek and Hyperdrive Mechanisms (in Mouse Meiosis)
Článek Elevated In Vivo Levels of a Single Transcription Factor Directly Convert Satellite Glia into Oligodendrocyte-like Cells
Článek Systemic Delivery of MicroRNA-101 Potently Inhibits Hepatocellular Carcinoma by Repressing Multiple Targets
Článek Pooled Sequencing of 531 Genes in Inflammatory Bowel Disease Identifies an Associated Rare Variant in and Implicates Other Immune Related Genes
Článek Abscission Is Regulated by the ESCRT-III Protein Shrub in Germline Stem Cells
Článek Temperature Stress Mediates Decanalization and Dominance of Gene Expression in
Článek Transcriptome Wide Annotation of Eukaryotic RNase III Reactivity and Degradation Signals
Článek The Exosome Component Rrp6 Is Required for RNA Polymerase II Termination at Specific Targets of the Nrd1-Nab3 Pathway
Článek Sex-specific -regulatory Variation on the X Chromosome
Článek Regulation of Toll-like Receptor Signaling by the SF3a mRNA Splicing Complex
Článek Modeling of the Human Alveolar Rhabdomyosarcoma Chromosome Translocation in Mouse Myoblasts Using CRISPR-Cas9 Nuclease
Článek Asymmetry of the Budding Yeast Tem1 GTPase at Spindle Poles Is Required for Spindle Positioning But Not for Mitotic Exit
Článek TIM Binds Importin α1, and Acts as an Adapter to Transport PER to the Nucleus
Článek Antagonistic Roles for KNOX1 and KNOX2 Genes in Patterning the Land Plant Body Plan Following an Ancient Gene Duplication
Článek The Genetic Architecture of the Genome-Wide Transcriptional Response to ER Stress in the Mouse
Článek Fatty Acid Synthase Cooperates with Glyoxalase 1 to Protect against Sugar Toxicity
Článek Region-Specific Activation of mRNA Translation by Inhibition of Bruno-Mediated Repression
Článek An Essential Role of the Arginine Vasotocin System in Mate-Guarding Behaviors in Triadic Relationships of Medaka Fish ()
Článek Interaction between the tRNA-Binding and C-Terminal Domains of Yeast Gcn2 Regulates Kinase Activity In Vivo
Článek Hyper-Acetylation of Histone H3K56 Limits Break-Induced Replication by Inhibiting Extensive Repair Synthesis
Článek Prodomain Removal Enables Neto to Stabilize Glutamate Receptors at the Neuromuscular Junction
Článek Recent Selective Sweeps in North American Show Signatures of Soft Sweeps
Článek Identification and Functional Analysis of Healing Regulators in
Článek A Multi-Megabase Copy Number Gain Causes Maternal Transmission Ratio Distortion on Mouse Chromosome 2
Článek Drosophila Casein Kinase I Alpha Regulates Homolog Pairing and Genome Organization by Modulating Condensin II Subunit Cap-H2 Levels
Článek The Hippo Pathway Regulates Homeostatic Growth of Stem Cell Niche Precursors in the Ovary
Článok vyšiel v časopise

PLOS Genetics

2015 Číslo 2
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

nový kurz
Autori: doc. MUDr. David Zemánek, Ph.D., MUDr. Anna Chaloupka, Ph.D.
Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#