In vivo determination of mitochondrial function using luciferase-expressing caenorhabditis elegans: Contribution of oxidative phosphorylation, glycolysis, and fatty acid oxidation to toxicant-induced dysfunction

Current Protocols in Toxicology

Volumn 2016, Issue , 2016, Pages 1-22

  Luz, Anthony L ^a   Lagido, Cristina ^b   Hirschey, Matthew D ^c   Meyer, Joel N ^a  

^a DUKE UNIVERSITY   (United States)

^b UNIVERSITY OF ABERDEEN   (United Kingdom)

^c DUKE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Caenorhabditis elegans; Fatty acid oxidation; Glycolysis; Mitochondrial toxicity; Oxidative phosphorylation; PE255; PE327

Indexed keywords

ADENOSINE TRIPHOSPHATE; DEOXYGLUCOSE; HYPOCHLORITE SODIUM; LUCIFERASE; PERHEXILINE; TOXIC SUBSTANCE; FATTY ACID; FIREFLY LUCIFERASE; GREEN FLUORESCENT PROTEIN; HYBRID PROTEIN; XENOBIOTIC AGENT;

AGE; ARTICLE; CAENORHABDITIS ELEGANS; CELL CULTURE; CELL DIFFERENTIATION; CELL FUNCTION; CYTOTOXICITY; DRUG EXPOSURE; FATTY ACID OXIDATION; GENETIC BACKGROUND; GLYCOLYSIS; IN VIVO STUDY; MICROPLATE READER; MITOCHONDRIAL ENERGY TRANSFER; MITOCHONDRIAL TOXICITY; MITOCHONDRION; NEMATODE; NONHUMAN; OXIDATIVE PHOSPHORYLATION; PRIORITY JOURNAL; RESPIRATORY CHAIN; STEADY STATE; TIME FACTOR; ANIMAL; DEVICES; DRUG EFFECTS; ENERGY METABOLISM; ENZYMOLOGY; GENETICS; GROWTH, DEVELOPMENT AND AGING; KINETICS; LUMINESCENCE; METABOLISM; OXIDATION REDUCTION REACTION; PROCEDURES; REPORTER GENE; TOXICITY TESTING; TRANSGENIC ANIMAL;

ADENOSINE TRIPHOSPHATE; ANIMALS; ANIMALS, GENETICALLY MODIFIED; CAENORHABDITIS ELEGANS; ENERGY METABOLISM; FATTY ACIDS, NONESTERIFIED; GENES, REPORTER; GLYCOLYSIS; GREEN FLUORESCENT PROTEINS; KINETICS; LUCIFERASES, FIREFLY; LUMINESCENT MEASUREMENTS; MITOCHONDRIA; OXIDATION-REDUCTION; OXIDATIVE PHOSPHORYLATION; RECOMBINANT FUSION PROTEINS; TOXICITY TESTS, ACUTE; XENOBIOTICS;

EID: 85022197589     PISSN: 19349254     EISSN: 19349262     Source Type: Journal    
DOI: 10.1002/cptx.10     Document Type: Article

References (55)

1. Backer, J. and Weinstein, I. 1980. Mitochondrial DNA is a major cellular target for a dihydrodiolepoxide derivative of benzo [a] pyrene. Science 209:297-299. doi: 10.1126/science.6770466.
2. Baysal, B.E., Ferrell, R.E., Willett-Brozick, J.E., Lawrence, E.C., Myssiorek, D., Bosch, A., van der Mey, A., Taschner, P.E., Rubinstein, W.S., and Myers, E.N. 2000. Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma. Science 287:848-851.
3. Beal, M.F. 2005. Mitochondria take center stage in aging and neurodegeneration. Ann. Neurol. 58:495-505. doi: 10.1002/ana.20624
4. Beanan, M.J. and Strome, S. 1992. Characterization of a germ-line proliferation mutation in C. elegans. Development 116:755-766.
5. Bess, A.S., Crocker, T.L., Ryde, I.T., and Meyer, J.N. 2012. Mitochondrial dynamics and autophagy aid in removal of persistent mitochondrial DNA damage in Caenorhabditis elegans. Nucleic Acids Res. 40:7916-7931. doi: 10.1093/nar/gks532.
6. Bess, A.S., Leung, M.C., Ryde, I.T., Rooney, J.P., Hinton, D.E., and Meyer, J.N. 2013. Effects of mutations in mitochondrial dynamicsrelated genes on the mitochondrial response to ultraviolet C radiation in developing Caenorhabditis elegans. Worm 2(1):e23763. doi: 10.4161/worm.23763.
7. Bodhicharla, R., Ryde, I.T., Prasad, G., and Meyer, J.N. 2014. The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induces mitochondrial and nuclear DNA damage in Caenorhabditis elegans. Environ. Mol. Mutagen. 55:43-50. doi: 10.1002/em.21815.
8. Boyd, W., Smith, M., Co, C., Pirone, J., Rice, J., Shockley, K., and Freedman, J. 2016. Developmental effects of the ToxCastTM Phase I and II chemicals in Caenorhabditis elegans and corresponding responses in zebrafish, rats, and rabbits. Environ. Health Perspect. 124:586-593.
9. Braeckman, B.P., Houthoofd, K., and Vanfleteren, J.R. 2009. Intermediary metabolism. WormBook. doi: 10.1895/wormbook.1.146.1 ISBN/ISSN: 1551-8507. Available at http://www.wormbook.org/chapters/www_intermetab olism/intermetabolism.pdf.
10. Braeckman, B.P., Houthoofd, K., De Vreese, A., and Vanfleteren, J.R. 2002. Assaying metabolic activity in ageing Caenorhabditis elegans. Mech. Ageing Dev. 123:105-119.
11. Brys, K., Castelein, N., Matthijssens, F., Vanfleteren, J.R., and Braeckman, B.P. 2010. Disruption of insulin signalling preserves bioenergetic competence of mitochondria in ageing Caenorhabditis elegans. BMC Biol. 8:91. doi: 10.1186/1741-7007-8-91.
12. Bugger, H. 2008. Molecular mechanisms for myocardial mitochondrial dysfunction in the metabolic syndrome. Clin. Sci. 114:195-210. doi: 10.1042/CS20070166.
13. Chan, D.C. 2012. Fusion and fission: Interlinked processes critical for mitochondrial health. Annu. Rev. Genet. 46:265-287. doi: 10.1146/annurev-genet-110410-132529.
14. Duchen, M.R. 2000. Mitochondria and calcium: From cell signalling to cell death. J. Physiol. 529:57-68. doi: 10.1111/j.1469-7793.2000.00057.x.
15. Dykens, J.A. and Will, Y. 2007. The significance of mitochondrial toxicity testing in drug development. Drug Discov. Today 12:777-785.
16. Guan, M.-X. 2011. Mitochondrial 12S rRNA mutations associated with aminoglycoside ototoxicity. Mitochondrion 11:237-245. doi: 10.1016/j.mito.2010.10.006.
17. Kamath, R.S., Fraser, A.G., Dong, Y., Poulin, G., Durbin, R., Gotta, M., Kanapin, A., Le Bot, N., Moreno, S., and Sohrmann, M. 2003. Systematic functional analysis of the Caenorhabditis elegans genome using RNAi. Nature 421:231-237. doi: 10.1038/nature01278.
18. Kennedy, J.A., Unger, S.A., and Horowitz, J.D. 1996. Inhibition of carnitine palmitoyltransferase-1 in rat heart and liver by perhexiline and amiodarone. Biochem. Pharmacol. 52:273-280. doi: 10.1016/0006-2952(96)00204-3.
19. Kjekshus, J.K. and Mjøs, O.D. 1972. Effect of free fatty acids on myocardial function and metabolism in the ischemic dog heart. Eur. J. Clin. Invest. 51:1767. doi: 10.1172/JCI106978.
20. Krijgsveld, J., Ketting, R.F., Mahmoudi, T., Johansen, J., Artal-Sanz, M., Verrijzer, C.P., Plasterk, R.H., and Heck, A.J. 2003. Metabolic labeling of C. elegans and D. melanogaster for quantitative proteomics. Nat. Biotechnol. 21:927-931. doi: 10.1038/nbt848.
21. Lagido, C., McLaggan, D., and Glover, L.A. 2015. A screenable in vivo assay for mitochondrial modulators using transgenic bioluminescent Caenorhabditis elegans. J. Vis. Exp. 104:e53083. doi: 10.3791/53083.
22. Lagido, C., Pettitt, J., Flett, A., and Glover, L.A. 2008. Bridging the phenotypic gap: Real-time assessment of mitochondrial function and metabolism of the nematode Caenorhabditis elegans. BMC Physiol. 8:7. doi: 10.1186/1472-6793-8-7.
23. Lagido, C., Pettitt, J., Porter, A., Paton, G., and Glover, L. 2001. Development and application of bioluminescent Caenorhabditis elegans as multicellular eukaryotic biosensors. FEBS Lett. 493:36-39. doi: 10.1016/S0014-5793(01)02271-2.
24. Lagido, C., McLaggan, D., Flett, A., Pettitt, J., and Glover, L.A. 2009. Rapid sublethal toxicity assessment using bioluminescent Caenorhabditis elegans, a novel whole-animal metabolic biosensor. Toxicol. Sci. 109:88-95. doi: 10.1093/toxsci/kfp058.
25. Leung, M.C., Rooney, J.P., Ryde, I.T., Bernal, A.J., Bess, A.S., Crocker, T.L., Ji, A.Q., and Meyer, J.N. 2013. Effects of early life exposure to ultraviolet C radiation on mitochondrial DNA content, transcription, ATP production, and oxygen consumption in developing Caenorhabditis elegans. BMC Pharmacol. Toxicol. 14:9. doi: 10.1186/2050-6511-14-9.
26. Lewis, J.A. and Fleming, J.T. 1995. Basic culture methods. Methods Cell Biol. 48:3-29. doi: 10.1016/S0091-679X(08)61381-3.
27. Lin, M.T. and Beal, M.F. 2006. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 443:787-795. doi: 10.1038/nature05292.
28. Liu, Z. and Butow, R.A. 2006. Mitochondrial retrograde signaling. Annu. Rev. Genet. 40:159-185. doi: 10.1146/annurev.genet.40.110405.090613.
29. Luz, A.L., Rooney, J.P., Kubik, L.L., Gonzalez, C.P., Song, D.H., and Meyer, J.N. 2015a. Mitochondrial morphology and fundamental parameters of the mitochondrial respiratory chain are altered in Caenorhabditis elegans strains deficient in mitochondrial dynamics and homeostasis processes. PloS One 10:e0130940. doi: 10.1371/journal.pone.0130940.
30. Luz, A.L., Smith, L.L., Rooney, J.P., and Meyer, J.N. 2015b. Seahorse Xfe24 extracellular flux analyzer-based analysis of cellular respiration in Caenorhabditis elegans. Curr. Protoc. Toxicol. 66:25.7.1-25.7.15. doi: 10.1002/0471140856.tx2507s66.
31. Luz, A.L., Godebo, T., Bhatt, D.P., Ilkayeva, O.R., Maurer, L.L., Hirschey, M.D., and Meyer, J.N. 2016. Arsenite uncouples mitochondrial respiration and induces a Warburg-like effect in Caenorhabditis elegans. Toxicol Sci. In Press. McBride, H.M., Neuspiel, M., and Wasiak, S. 2006. Mitochondria: More than just a powerhouse. Curr. Biol. 16:R551-R560. doi: 10.1016/j.cub.2006.06.054.
32. McLaggan, D., Amezaga, M.R., Petra, E., Frost, A., Duff, E.I., Rhind, S.M., Fowler, P.A., Glover, L.A., and Lagido, C. 2012. Impact of sublethal levels of environmental pollutants found in sewage sluge on a novel Caenorhabditis elegans model biosensor. PloS one 7:e46503. doi: 10.1371/journal.pone.0046503.
33. Meyer, J.N., Leung, M.C., Rooney, J.P., Sendoel, A., Hengartner, M.O., Kisby, G.E., and Bess, A.S. 2013. Mitochondria as a target of environmental toxicants. Toxicol. Sci. 134:1-17. doi: 10.1093/toxsci/kft102.
34. Mjos, O. and Kjekshus, J. 1971. Increased local metabolic rate by free fatty acids in the intact dog heart. Scand. J. Clin. Lab. Res. Investig. 28:389-393. doi: 10.3109/00365517109095714.
35. Olmedo, M., Geibel, M., Artal-Sanz, M., and Merrow, M. 2015. A high-throughput method for the analysis of larval developmental phenotypes in Caenorhabditis elegans. Genetics 201:443-448. doi: 10.1534/genetics.115.179242.
36. Poirier, M.C., Gibbons, A.T., Rugeles, M.T., Andre-Schmutz, I., and Blanche, S. 2015. Fetal consequences of maternal antiretroviral nucleoside reverse transcriptase inhibitor use in human and nonhuman primate pregnancy. Curr. Opin. Pediatr. 27:233-239. doi: 10.1097/MOP.0000000000000193.
37. Ratnappan, R., Amrit, F.R., Chen, S.-W., Gill, H., Holden, K., Ward, J., Yamamoto, K.R., Olsen, C.P., and Ghazi, A. 2014. Germline signals deploy NHR-49 to modulate fatty-acid β-oxidation and desaturation in somatic tissues of C. elegans. PLoS Genet. 10:e1004829. doi: 10.1371/journal.pgen.1004829.
38. Robey, R.B., Weisz, J., Kuemmerle, N., Salzberg, A.C., Berg, A., Brown, D.G., Kubik, L., Palorini, R., Al-Mulla, F., and Al-Temaimi, R. 2015. Metabolic reprogramming and dysregulated metabolism: Cause, consequence and/or enabler of environmental carcinogenesis? Carcinogenesis 36:S203-S231. doi: 10.1093/carcin/bgv037.
39. Rooney, J., Luz, A., Gonzalez-Hunt, C., Bodhicharla, R., Ryde, I., Anbalagan, C., andMeyer, J. 2014. Effects of 5_-fluoro-2-deoxyuridine on mitochondrial biology in Caenorhabditis elegans. Exp. Gerontol. 56:69-76. doi: 10.1016/j.exger.2014.03.021.
40. Schulz, T.J., Zarse, K., Voigt, A., Urban, N., Birringer, M., and Ristow, M. 2007. Glucose restriction extends Caenorhabditis elegans life span by inducing mitochondrial respiration and increasing oxidative stress. Cell Metab. 6:280-293. doi: 10.1016/j.cmet.2007.08.011.
41. Shukla, K., Ferraris, D.V., Thomas, A.G., Stathis, M., Duvall, B., Delahanty, G., Alt, J., Rais, R., Rojas, C., and Gao, P. 2012. Design, synthesis, and pharmacological evaluation of bis-2-(5-phenylacetamido-1, 2, 4-thiadiazol-2-yl) ethyl sulfide 3 (BPTES) analogs as glutaminase inhibitors. J. Med. Chem. 55:10551-10563. doi: 10.1021/jm301191p.
42. Stanley, W.C., Lopaschuk, G.D., Hall, J.L., and Mc-Cormack, J.G. 1997. Regulation of myocardial carbohydrate metabolism under normal and ischaemic conditions. Cardiovasc. Res. 33:243-257. doi: 10.1016/S0008-6363(96)00245-3.
43. Stiernagle, T. 1999. Maintenance of C. elegans. Available at http://wormbook.org/chapters/www_strainmaintain/strainmaintain.pdf.
44. Susin, S.A., Lorenzo, H.K., Zamzami, N., Marzo, I., Snow, B.E., Brothers, G.M., Mangion, J., Jacotot, E., Costantini, P., and Loeffler, M. 1999. Molecular characterization of mitochondrial apoptosis-inducing factor. Nature 397:441-446. doi: 10.1038/17135.
45. Tanner, C.M., Kamel, F., Ross, G., Hoppin, J.A., Goldman, S.M., Korell, M., Marras, C., Bhudhikanok, G.S., Kasten, M., and Chade, A.R. 2011. Rotenone, paraquat, and Parkinson’s disease. Environ. Health Perspect. 119:866-872. doi: 10.1289/ehp.1002839.
46. Taylor, C.M., Wang, Q., Rosa, B.A., Huang, S., Powell, K., Schedl, T., Pearce, E.J., Abubucker, S., and Mitreva, M. 2013. Discovery of anthelmintic drug targets and drugs using chokepoints in nematode metabolic pathways. PLoS Pathog. 9:e1003505. doi: 10.1371/journal.ppat.1003505.
47. Thompson, O., Edgley, M., Strasbourger, P., Flibotte, S., Ewing, B., Adair, R., Au, V., Chaudhry, I., Fernando, L., and Hutter, H. 2013. The million mutation project: A new approach to genetics in Caenorhabditis elegans. Genome Res. 23:1749-1762. doi: 10.1101/gr.157651.113.
48. Thorn, M. 1953. Inhibition by malonate of succinic dehydrogenase in heart-muscle preparations. Biochem. J. 54:540. doi: 10.1042/bj0540540.
49. Tsang, W.Y. and Lemire, B.D. 2003. The role of mitochondria in the life of the nematode, Caenorhabditis elegans. Biochim. Biophys. Acta (BBA) 1638:91-105. doi: 10.1016/S0925-4439(03)00079-6.
50. Wallace, D.C. 2012. Mitochondria and cancer. Nat. Rev. Cancer 12:685-698. doi: 10.1038/nrc3365.
51. Weber, C.I. 1991. Methods for measuring the acute toxicity of effluents and receiving waters to freshwater and marine organisms. Environmental Monitoring Systems Laboratory, Office of Research and Development, U.S. Environmental Protection Agency.
52. Yan, H., Parsons, D.W., Jin, G., McLendon, R., Rasheed, B.A., Yuan, W., Kos, I., Batinic-Haberle, I., Jones, S., and Riggins, G.J. 2009. IDH1 and IDH2 mutations in gliomas. N. Engl. J. Med. 360:765-773. doi: 10.1056/NEJMoa0808710.
53. Zhao, F., Malm, S.W., Hinchman, A.N., Li, H., Beeks, C.G., and Klimecki, W.T. 2014. Arsenite-induced pseudo-hypoxia results in loss of anchorage-dependent growth in BEAS-2B pulmonary epithelial cells. PloS One 9:e114549. doi: 10.1371/journal.pone.0114549.
54. Zheng, S.-Q., Ding, A.-J., Li, G.-P., Wu, G.-S., and Luo, H.-R. 2013. Drug absorption efficiency in Caenorhabditis elegans delivered by different methods. PloS One 8:e56877. doi: 10.1371/journal.pone.0056877.
55. Zubovych, I.O., Straud, S., and Roth, M.G. 2010. Mitochondrial dysfunction confers resistance to multiple drugs in Caenorhabditis elegans. Mol. Biol. Cell 21:956-969. doi: 10.1091/mbc.E09-08-0673.