The paradox of mitochondrial dysfunction and extended longevity

Experimental Gerontology

Volumn 56, Issue , 2014, Pages 221-233

  Munkácsy, Erin ^a   Rea, Shane L ^a  

^a UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO   (United States)

Author keywords

Aging; C. elegans; Lifespan; Metabolism; Mit mutant; Mitochondria

Indexed keywords

CHAPERONE; CYTOCHROME C OXIDASE; ELECTRON TRANSFERRING FLAVOPROTEIN; MANGANESE SUPEROXIDE DISMUTASE; REACTIVE OXYGEN METABOLITE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE; SUCCINATE DEHYDROGENASE (UBIQUINONE); TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR CEP 1; TRANSCRIPTION FACTOR DAF 16; TRICARBOXYLIC ACID; UBIQUINOL CYTOCHROME C REDUCTASE; UBIQUINONE; UNCLASSIFIED DRUG; MITOCHONDRIAL PROTEIN;

AUTOPHAGY; CAENORHABDITIS ELEGANS; CEP 1 GENE; CITRIC ACID CYCLE; CLK 1 GENE; DAF 2 GENE; DISORDERS OF MITOCHONDRIAL FUNCTIONS; ENZYME DEFECT; EVOLUTIONARY ADAPTATION; GENE; GENE INACTIVATION; GENE TARGETING; HUMAN; INTRACELLULAR SIGNALING; ISP 1 GENE; LIFE EXTENSION; LIFESPAN; LONGEVITY; MITOCHONDRIAL RESPIRATION; MITOPHAGY; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROTEIN UNFOLDING; RESPIRATORY CHAIN; REVIEW; RNA INTERFERENCE; SOD 2 GENE; UNFOLDED PROTEIN RESPONSE; AGE; AGING; ANIMAL; ANIMAL MODEL; ENERGY METABOLISM; GENETICS; GENOTYPE; METABOLISM; MITOCHONDRION; OXIDATIVE STRESS; PATHOLOGY;

AGE FACTORS; AGING; ANIMALS; AUTOPHAGY; CAENORHABDITIS ELEGANS; ENERGY METABOLISM; GENOTYPE; HUMANS; LONGEVITY; MITOCHONDRIA; MITOCHONDRIAL PROTEINS; MODELS, ANIMAL; OXIDATIVE STRESS; PHENOTYPE; REACTIVE OXYGEN SPECIES; TRANSCRIPTION FACTORS; UNFOLDED PROTEIN RESPONSE;

EID: 84901756876     PISSN: 05315565     EISSN: 18736815     Source Type: Journal    
DOI: 10.1016/j.exger.2014.03.016     Document Type: Review

References (108)

1. Acin-Perez R., Bayona-Bafaluy M.P., Fernandez-Silva P., Moreno-Loshuertos R., Perez-Martos A., Bruno C., Moraes C.T., Enriquez J.A. Respiratory complex III is required to maintain complex I in mammalian mitochondria. Mol. Cell 2004, 13:805-815.
2. Altarejos J.Y., Montminy M. CREB and the CRTC co-activators: sensors for hormonal and metabolic signals. Nat. Rev. Mol. Cell Biol. 2011, 12:141-151.
3. Altun-Gultekin Z., Andachi Y., Tsalik E.L., Pilgrim D., Kohara Y., Hobert O. A regulatory cascade of three homeobox genes, ceh-10, ttx-3 and ceh-23, controls cell fate specification of a defined interneuron class in C. elegans. Development 2001, 128:1951-1969.
4. An J.H., Blackwell T.K. SKN-1 links C. elegans mesendodermal specification to a conserved oxidative stress response. Genes Dev. 2003, 17:1882-1893.
5. Andziak B., O'Connor T.P., Qi W., DeWaal E.M., Pierce A., Chaudhuri A.R., Van Remmen H., Buffenstein R. High oxidative damage levels in the longest-living rodent, the naked mole-rat. Aging Cell 2006, 5:463-471.
6. Baker B.M., Nargund A.M., Sun T., Haynes C.M. Protective coupling of mitochondrial function and protein synthesis via the eIF2alpha kinase GCN-2. PLoS Genet. 2012, 8:e1002760.
7. Benedetti C., Haynes C.M., Yang Y., Harding H.P., Ron D. Ubiquitin-like protein 5 positively regulates chaperone gene expression in the mitochondrial unfolded protein response. Genetics 2006, 174:229-239.
8. Bishop N.A., Guarente L. Two neurons mediate diet-restriction-induced longevity in C. elegans. Nature 2007, 447:545-549.
9. Butler J.A., Ventura N., Johnson T.E., Rea S.L. Long-lived mitochondrial (Mit) mutants of Caenorhabditis elegans utilize a novel metabolism. FASEB J. 2010, 24:4977-4988.
10. Butler J.A., Mishur R.J., Bokov A.F., Hakala K.W., Weintraub S.T., Rea S.L. Profiling the anaerobic response of C. elegans using GC-MS. PLoS ONE 2012, 7:e46140.
11. Butler J.A., Mishur R.J., Bhaskaran S., Rea S.L. A metabolic signature for long life in the Caenorhabditis elegans Mit mutants. Aging Cell 2013, 12:130-138.
12. Chen D., Thomas E.L., Kapahi P. HIF-1 modulates dietary restriction-mediated lifespan extension via IRE-1 in Caenorhabditis elegans. PLoS Genet. 2009, 5:e1000486.
13. Chowdhury R., Yeoh K.K., Tian Y.M., Hillringhaus L., Bagg E.A., Rose N.R., Leung I.K., Li X.S., Woon E.C., Yang M., McDonough M.A., King O.N., Clifton I.J., Klose R.J., Claridge T.D., Ratcliffe P.J., Schofield C.J., Kawamura A. The oncometabolite 2-hydroxyglutarate inhibits histone lysine demethylases. EMBO Rep. 2011, 12:463-469.
14. Cristina D., Cary M., Lunceford A., Clarke C., Kenyon C. A regulated response to impaired respiration slows behavioral rates and increases lifespan in Caenorhabditis elegans. PLoS Genet. 2009, 5:e1000450.
15. Cunliffe C.J., Franklin T.J., Hales N.J., Hill G.B. Novel inhibitors of prolyl 4-hydroxylase. 3. Inhibition by the substrate analogue N-oxaloglycine and its derivatives. J. Med. Chem. 1992, 35:2652-2658.
16. Dell'agnello C., Leo S., Agostino A., Szabadkai G., Tiveron C., Zulian A., Prelle A., Roubertoux P., Rizzuto R., Zeviani M. Increased longevity and refractoriness to Ca(2+)-dependent neurodegeneration in Surf1 knockout mice. Hum. Mol. Genet. 2007, 16:431-444.
17. Dillin A., Hsu A.L., Arantes-Oliveira N., Lehrer-Graiwer J., Hsin H., Fraser A.G., Kamath R.S., Ahringer J., Kenyon C. Rates of behavior and aging specified by mitochondrial function during development. Science 2002, 298:2398-2401.
18. Durieux J., Wolff S., Dillin A. The cell-non-autonomous nature of electron transport chain-mediated longevity. Cell 2011, 144:79-91.
19. Epstein A.C., Gleadle J.M., McNeill L.A., Hewitson K.S., O'Rourke J., Mole D.R., Mukherji M., Metzen E., Wilson M.I., Dhanda A., Tian Y.M., Masson N., Hamilton D.L., Jaakkola P., Barstead R., Hodgkin J., Maxwell P.H., Pugh C.W., Schofield C.J., Ratcliffe P.J. C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation. Cell 2001, 107:43-54.
20. Falk M.J., Zhang Z., Rosenjack J.R., Nissim I., Daikhin E., Nissim I., Sedensky M.M., Yudkoff M., Morgan P.G. Metabolic pathway profiling of mitochondrial respiratory chain mutants in C. elegans. Mol. Genet. Metab. 2008, 93:388-397.
21. Feng J., Bussiere F., Hekimi S. Mitochondrial electron transport is a key determinant of life span in Caenorhabditis elegans. Dev. Cell 2001, 1:633-644.
22. Genova M.L., Lenaz G. Functional role of mitochondrial respiratory supercomplexes. Biochim. Biophys. Acta 2013, 1837:427-443.
23. Grad L.I., Lemire B.D. Mitochondrial complex I mutations in Caenorhabditis elegans produce cytochrome c oxidase deficiency, oxidative stress and vitamin-responsive lactic acidosis. Hum. Mol. Genet. 2004, 13:303-314.
24. Greer E.L., Dowlatshahi D., Banko M.R., Villen J., Hoang K., Blanchard D., Gygi S.P., Brunet A. An AMPK-FOXO pathway mediates longevity induced by a novel method of dietary restriction in C. elegans. Curr. Biol. 2007, 17:1646-1656.
25. Grimm S. Respiratory chain complex II as general sensor for apoptosis. Biochim. Biophys. Acta 2013, 1827:565-572.
26. Hansen M., Hsu A.L., Dillin A., Kenyon C. New genes tied to endocrine, metabolic, and dietary regulation of lifespan from a Caenorhabditis elegans genomic RNAi screen. PLoS Genet. 2005, 1:119-128.
27. Harman D. Aging: a theory based on free radical and radiation chemistry. J. Gerontol. 1956, 11:298-300.
28. Hartman P.S., Ishii N., Kayser E.B., Morgan P.G., Sedensky M.M. Mitochondrial mutations differentially affect aging, mutability and anesthetic sensitivity in Caenorhabditis elegans. Mech. Ageing Dev. 2001, 122:1187-1201.
29. Haynes C.M., Petrova K., Benedetti C., Yang Y., Ron D. ClpP mediates activation of a mitochondrial unfolded protein response in C. elegans. Dev. Cell 2007, 13:467-480.
30. Haynes C.M., Yang Y., Blais S.P., Neubert T.A., Ron D. The matrix peptide exporter HAF-1 signals a mitochondrial UPR by activating the transcription factor ZC376.7 in C. elegans. Mol. Cell 2010, 37:529-540.
31. Haynes C.M., Fiorese C.J., Lin Y.F. Evaluating and responding to mitochondrial dysfunction: the mitochondrial unfolded-protein response and beyond. Trends Cell Biol. 2013, 23:311-318.
32. Honjoh S., Yamamoto T., Uno M., Nishida E. Signalling through RHEB-1 mediates intermittent fasting-induced longevity in C. elegans. Nature 2009, 457:726-730.
33. Houtkooper R.H., Mouchiroud L., Ryu D., Moullan N., Katsyuba E., Knott G., Williams R.W., Auwerx J. Mitonuclear protein imbalance as a conserved longevity mechanism. Nature 2013, 497:451-457.
34. Hutchinson S.E., Leveridge M.V., Heathcote M.L., Francis P., Williams L., Gee M., Munoz-Muriedas J., Leavens B., Shillings A., Jones E., Homes P., Baddeley S., Chung C.W., Bridges A., Argyrou A. Enabling lead discovery for histone lysine demethylases by high-throughput RapidFire mass spectrometry. J. Biomol. Screen. 2012, 17:39-48.
35. Hwang A.B., Lee S.J. Regulation of life span by mitochondrial respiration: the HIF-1 and ROS connection. Aging 2011, 3:304-310.
36. Ichimiya H., Huet R.G., Hartman P., Amino H., Kita K., Ishii N. Complex II inactivation is lethal in the nematode Caenorhabditis elegans. Mitochondrion 2002, 2:191-198.
37. Ishii N., Takahashi K., Tomita S., Keino T., Honda S., Yoshino K., Suzuki K. A methyl viologen-sensitive mutant of the nematode Caenorhabditis elegans. Mutat. Res. 1990, 237:165-171.
38. 2 sensing. Science 2001, 292:464-468.
39. Jiang H., Guo R., Powell-Coffman J.A. The Caenorhabditis elegans hif-1 gene encodes a bHLH-PAS protein that is required for adaptation to hypoxia. Proc. Natl. Acad. Sci. U. S. A. 2001, 98:7916-7921.
40. Kahn N.W., Rea S.L., Moyle S., Kell A., Johnson T.E. Proteasomal dysfunction activates the transcription factor SKN-1 and produces a selective oxidative-stress response in Caenorhabditis elegans. Biochem. J. 2008, 409:205-213.
41. Kamath R.S., Fraser A.G., Dong Y., Poulin G., Durbin R., Gotta M., Kanapin A., Le Bot N., Moreno S., Sohrmann M., Welchman D.P., Zipperlen P., Ahringer J. Systematic functional analysis of the Caenorhabditis elegans genome using RNAi. Nature 2003, 421:231-237.
42. Kang C., You Y.J., Avery L. Dual roles of autophagy in the survival of Caenorhabditis elegans during starvation. Genes Dev. 2007, 21:2161-2171.
43. Khan M.H., Ligon M., Hussey L.R., Hufnal B., Farber R., Munkacsy E., Rodriguez A., Dillow A., Kahlig E., Rea S.L. TAF-4 is required for the life extension of isp-1, clk-1 and tpk-1 Mit mutants. Aging 2013, 5:741-758.
44. Kim Y., Sun H. Functional genomic approach to identify novel genes involved in the regulation of oxidative stress resistance and animal lifespan. Aging Cell 2007, 6:489-503.
45. Kourtis N., Tavernarakis N. Autophagy and cell death in model organisms. Cell Death Differ. 2009, 16:21-30.
46. Kuang J., Ebert P.R. The failure to extend lifespan via disruption of complex II is linked to preservation of dynamic control of energy metabolism. Mitochondrion 2012, 12:280-287.
47. Labuschagne C.F., Stigter E.C., Hendriks M.M., Berger R., Rokach J., Korswagen H.C., Brenkman A.B. Quantification of in vivo oxidative damage in Caenorhabditis elegans during aging by endogenous F3-isoprostane measurement. Aging Cell 2013, 12:214-223.
48. Lakowski B., Hekimi S. Determination of life-span in Caenorhabditis elegans by four clock genes. Science 1996, 272:1010-1013.
49. Lane N., Martin W. The energetics of genome complexity. Nature 2010, 467:929-934.
50. Lapierre L.R., Melendez A., Hansen M. Autophagy links lipid metabolism to longevity in C. elegans. Autophagy 2012, 8:144-146.
51. Lapierre L.R., De Magalhaes Filho C.D., McQuary P.R., Chu C.C., Visvikis O., Chang J.T., Gelino S., Ong B., Davis A.E., Irazoqui J.E., Dillin A., Hansen M. The TFEB orthologue HLH-30 regulates autophagy and modulates longevity in Caenorhabditis elegans. Nat. Commun. 2013, 4:2267.
52. Lee S.S., Lee R.Y., Fraser A.G., Kamath R.S., Ahringer J., Ruvkun G. A systematic RNAi screen identifies a critical role for mitochondria in C. elegans longevity. Nat. Genet. 2003, 33:40-48.
53. Lee S.J., Hwang A.B., Kenyon C. Inhibition of respiration extends C. elegans life span via reactive oxygen species that increase HIF-1 activity. Curr. Biol. 2010, 20:2131-2136.
54. Limongelli A., Schaefer J., Jackson S., Invernizzi F., Kirino Y., Suzuki T., Reichmann H., Zeviani M. Variable penetrance of a familial progressive necrotising encephalopathy due to a novel tRNA(Ile) homoplasmic mutation in the mitochondrial genome. J. Med. Genet. 2004, 41:342-349.
55. Lin K., Dorman J.B., Rodan A., Kenyon C. daf-16: an HNF-3/forkhead family member that can function to double the life-span of Caenorhabditis elegans. Science 1997, 278:1319-1322.
56. Lionaki E., Markaki M., Tavernarakis N. Autophagy and ageing: insights from invertebrate model organisms. Ageing Res. Rev. 2013, 12:413-428.
57. Liu X., Jiang N., Hughes B., Bigras E., Shoubridge E., Hekimi S. Evolutionary conservation of the clk-1-dependent mechanism of longevity: loss of mclk1 increases cellular fitness and lifespan in mice. Genes Dev. 2005, 19:2424-2434.
58. Marino G., Ugalde A.P., Salvador-Montoliu N., Varela I., Quiros P.M., Cadinanos J., van der Pluijm I., Freije J.M., Lopez-Otin C. Premature aging in mice activates a systemic metabolic response involving autophagy induction. Hum. Mol. Genet. 2008, 17:2196-2211.
59. Masoro E.J. Hormesis and the antiaging action of dietary restriction. Exp. Gerontol. 1998, 33:61-66.
60. Miceli M.V., Jiang J.C., Tiwari A., Rodriguez-Quinones J.F., Jazwinski S.M. Loss of mitochondrial membrane potential triggers the retrograde response extending yeast replicative lifespan. Front. Genet. 2011, 2:102.
61. Mishur R.J., Butler J.A., Rea S.L. Exometabolomic mapping of Caenorhabditis elegans: a tool to noninvasively investigate aging. Methods Mol. Biol. 2013, 1048:195-213.
62. Miyadera H., Amino H., Hiraishi A., Taka H., Murayama K., Miyoshi H., Sakamoto K., Ishii N., Hekimi S., Kita K. Altered quinone biosynthesis in the long-lived clk-1 mutants of Caenorhabditis elegans. J. Biol. Chem. 2001, 276:7713-7716.
63. Nargund A.M., Pellegrino M.W., Fiorese C.J., Baker B.M., Haynes C.M. Mitochondrial import efficiency of ATFS-1 regulates mitochondrial UPR activation. Science 2012, 337:587-590.
64. O'Rourke E.J., Ruvkun G. MXL-3 and HLH-30 transcriptionally link lipolysis and autophagy to nutrient availability. Nat. Cell Biol. 2013, 15:668-676.
65. Pellegrino M.W., Nargund A.M., Haynes C.M. Signaling the mitochondrial unfolded protein response. Biochim. Biophys. Acta 2013, 1833:410-416.
66. Pujol C., Bratic-Hench I., Sumakovic M., Hench J., Mourier A., Baumann L., Pavlenko V., Trifunovic A. Succinate dehydrogenase upregulation destabilize complex I and limits the lifespan of gas-1 mutant. PLoS ONE 2013, 8:e59493.
67. Pyo J.O., Yoo S.M., Ahn H.H., Nah J., Hong S.H., Kam T.I., Jung S., Jung Y.K. Overexpression of Atg5 in mice activates autophagy and extends lifespan. Nat. Commun. 2013, 4:2300.
68. Rauthan M., Ranji P., Aguilera Pradenas N., Pitot C., Pilon M. The mitochondrial unfolded protein response activator ATFS-1 protects cells from inhibition of the mevalonate pathway. Proc. Natl. Acad. Sci. U. S. A. 2013, 110:5981-5986.
69. Ravikumar B., Duden R., Rubinsztein D.C. Aggregate-prone proteins with polyglutamine and polyalanine expansions are degraded by autophagy. Hum. Mol. Genet. 2002, 11:1107-1117.
70. Ray P.D., Huang B.W., Tsuji Y. Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell. Signal. 2012, 24:981-990.
71. Rea S.L. Metabolism in the Caenorhabditis elegans Mit mutants. Exp. Gerontol. 2005, 40:841-849.
72. Rea S.L., Ventura N., Johnson T.E. Relationship between mitochondrial electron transport chain dysfunction, development, and life extension in Caenorhabditis elegans. PLoS Biol. 2007, 5:e259.
73. Ristow M., Zarse K. How increased oxidative stress promotes longevity and metabolic health: the concept of mitochondrial hormesis (mitohormesis). Exp. Gerontol. 2010, 45:410-418.
74. Robida-Stubbs S., Glover-Cutter K., Lamming D.W., Mizunuma M., Narasimhan S.D., Neumann-Haefelin E., Sabatini D.M., Blackwell T.K. TOR signaling and rapamycin influence longevity by regulating SKN-1/Nrf and DAF-16/FoxO. Cell Metab. 2012, 15:713-724.
75. Schagger H., Pfeiffer K. The ratio of oxidative phosphorylation complexes I-V in bovine heart mitochondria and the composition of respiratory chain supercomplexes. J. Biol. Chem. 2001, 276:37861-37867.
76. Schiavi A., Torgovnick A., Kell A., Megalou E., Castelein N., Guccini I., Marzocchella L., Gelino S., Hansen M., Malisan F., Condo I., Bei R., Rea S.L., Braeckman B.P., Tavernarakis N., Testi R., Ventura N. Autophagy induction extends lifespan and reduces lipid content in response to frataxin silencing in C. elegans. Exp. Gerontol. 2013, 48:191-201.
77. Schmeisser S., Zarse K., Ristow M. Lonidamine extends lifespan of adult Caenorhabditis elegans by increasing the formation of mitochondrial reactive oxygen species. Horm. Metab. Res. 2011, 43:687-692.
78. Schmeisser S., Priebe S., Groth M., Monajembashi S., Hemmerich P., Guthke R., Platzer M., Ristow M. Neuronal ROS signaling rather than AMPK/sirtuin-mediated energy sensing links dietary restriction to lifespan extension. Mol. Metab. 2013, 2:92-102.
79. Schmeisser S., Schmeisser K., Weimer S., Groth M., Priebe S., Fazius E., Kuhlow D., Pick D., Einax J.W., Guthke R., Platzer M., Zarse K., Ristow M. Mitochondrial hormesis links low-dose arsenite exposure to lifespan extension. Aging Cell 2013, 12:508-517.
80. Senoo-Matsuda N., Yasuda K., Tsuda M., Ohkubo T., Yoshimura S., Nakazawa H., Hartman P.S., Ishii N. A defect in the cytochrome b large subunit in complex II causes both superoxide anion overproduction and abnormal energy metabolism in Caenorhabditis elegans. J. Biol. Chem. 2001, 276:41553-41558.
81. Senoo-Matsuda N., Hartman P.S., Akatsuka A., Yoshimura S., Ishii N. A complex II defect affects mitochondrial structure, leading to ced-3- and ced-4-dependent apoptosis and aging. J. Biol. Chem. 2003, 278:22031-22036.
82. Simmer F., Moorman C., van der Linden A.M., Kuijk E., van den Berghe P.V., Kamath R.S., Fraser A.G., Ahringer J., Plasterk R.H. Genome-wide RNAi of C. elegans using the hypersensitive rrf-3 strain reveals novel gene functions. PLoS Biol. 2003, 1:E12.
83. Simonsen A., Cumming R.C., Brech A., Isakson P., Schubert D.R., Finley K.D. Promoting basal levels of autophagy in the nervous system enhances longevity and oxidant resistance in adult Drosophila. Autophagy 2008, 4:176-184.
84. Sonnichsen B., Koski L.B., Walsh A., Marschall P., Neumann B., Brehm M., Alleaume A.M., Artelt J., Bettencourt P., Cassin E., Hewitson M., Holz C., Khan M., Lazik S., Martin C., Nitzsche B., Ruer M., Stamford J., Winzi M., Heinkel R., Roder M., Finell J., Hantsch H., Jones S.J., Jones M., Piano F., Gunsalus K.C., Oegema K., Gonczy P., Coulson A., Hyman A.A., Echeverri C.J. Full-genome RNAi profiling of early embryogenesis in Caenorhabditis elegans. Nature 2005, 434:462-469.
85. Suthammarak W., Yang Y.Y., Morgan P.G., Sedensky M.M. Complex I function is defective in complex IV-deficient Caenorhabditis elegans. J. Biol. Chem. 2009, 284:6425-6435.
86. Suthammarak W., Morgan P.G., Sedensky M.M. Mutations in mitochondrial complex III uniquely affect complex I in Caenorhabditis elegans. J. Biol. Chem. 2010, 285:40724-40731.
87. Suthammarak W., Somerlot B.H., Opheim E., Sedensky M., Morgan P.G. Novel Interactions between mitochondrial superoxide dismutases and the electron transport chain. Aging Cell 2013, 12:1132-1140.
88. Torgovnick A., Schiavi A., Testi R., Ventura N. A role for p53 in mitochondrial stress response control of longevity in C. elegans. Exp. Gerontol. 2010, 45:550-557.
89. Toth M.L., Sigmond T., Borsos E., Barna J., Erdelyi P., Takacs-Vellai K., Orosz L., Kovacs A.L., Csikos G., Sass M., Vellai T. Longevity pathways converge on autophagy genes to regulate life span in Caenorhabditis elegans. Autophagy 2008, 4:330-338.
90. Tsang W.Y., Lemire B.D. Mitochondrial genome content is regulated during nematode development. Biochem. Biophys. Res. Commun. 2002, 291:8-16.
91. Tullet J.M., Hertweck M., An J.H., Baker J., Hwang J.Y., Liu S., Oliveira R.P., Baumeister R., Blackwell T.K. Direct inhibition of the longevity-promoting factor SKN-1 by insulin-like signaling in C. elegans. Cell 2008, 132:1025-1038.
92. Twig G., Elorza A., Molina A.J., Mohamed H., Wikstrom J.D., Walzer G., Stiles L., Haigh S.E., Katz S., Las G., Alroy J., Wu M., Py B.F., Yuan J., Deeney J.T., Corkey B.E., Shirihai O.S. Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. EMBO J. 2008, 27:433-446.
93. Uno M., Honjoh S., Matsuda M., Hoshikawa H., Kishimoto S., Yamamoto T., Ebisuya M., Yamamoto T., Matsumoto K., Nishida E. A fasting-responsive signaling pathway that extends life span in C. elegans. Cell Rep. 2013, 3:79-91.
94. Van Raamsdonk J.M., Hekimi S. Deletion of the mitochondrial superoxide dismutase sod-2 extends lifespan in Caenorhabditis elegans. PLoS Genet. 2009, 5:e1000361.
95. Van Raamsdonk J.M., Hekimi S. FUdR causes a twofold increase in the lifespan of the mitochondrial mutant gas-1. Mech. Ageing Dev. 2011, 132:519-521.
96. Ventura N., Rea S.L. Caenorhabditis elegans mitochondrial mutants as an investigative tool to study human neurodegenerative diseases associated with mitochondrial dysfunction. Biotechnol. J. 2007, 2:584-595.
97. Ventura N., Rea S.L., Schiavi A., Torgovnick A., Testi R., Johnson T.E. p53/CEP-1 increases or decreases lifespan, depending on level of mitochondrial bioenergetic stress. Aging Cell 2009, 8:380-393.
98. Walker A.K., Rothman J.H., Shi Y., Blackwell T.K. Distinct requirements for C. elegans TAF(II)s in early embryonic transcription. EMBO J. 2001, 20:5269-5279.
99. Walter L., Baruah A., Chang H.W., Pace H.M., Lee S.S. The homeobox protein CEH-23 mediates prolonged longevity in response to impaired mitochondrial electron transport chain in C. elegans. PLoS Biol. 2011, 9:e1001084.
100. Wang M.C., O'Rourke E.J., Ruvkun G. Fat metabolism links germline stem cells and longevity in C. elegans. Science 2008, 322:957-960.
101. Wolff S., Dillin A. The trifecta of aging in Caenorhabditis elegans. Exp. Gerontol. 2006, 41:894-903.
102. Wong A., Boutis P., Hekimi S. Mutations in the clk-1 gene of Caenorhabditis elegans affect developmental and behavioral timing. Genetics 1995, 139:1247-1259.
103. Yang W., Hekimi S. Two modes of mitochondrial dysfunction lead independently to lifespan extension in Caenorhabditis elegans. Aging Cell 2010, 9:433-447.
104. Yang W., Li J., Hekimi S. 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 2007, 177:2063-2074.
105. Yoneda T., Benedetti C., Urano F., Clark S.G., Harding H.P., Ron D. Compartment-specific perturbation of protein handling activates genes encoding mitochondrial chaperones. J. Cell Sci. 2004, 117:4055-4066.
106. Zarse K., Schmeisser S., Groth M., Priebe S., Beuster G., Kuhlow D., Guthke R., Platzer M., Kahn C.R., Ristow M. Impaired insulin/IGF1 signaling extends life span by promoting mitochondrial l-proline catabolism to induce a transient ROS signal. Cell Metab. 2012, 15:451-465.
107. Zhang Y., Shao Z., Zhai Z., Shen C., Powell-Coffman J.A. The HIF-1 hypoxia-inducible factor modulates lifespan in C. elegans. PLoS ONE 2009, 4:e6348.
108. Zuryn S., Kuang J., Tuck A., Ebert P.R. Mitochondrial dysfunction in Caenorhabditis elegans causes metabolic restructuring, but this is not linked to longevity. Mech. Ageing Dev. 2010, 131:554-561.