Neuroligin-mediated neurodevelopmental defects are induced by mitochondrial dysfunction and prevented by lutein in C. elegans.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
12 05 2022
12 05 2022
Historique:
received:
30
06
2021
accepted:
09
04
2022
entrez:
13
5
2022
pubmed:
14
5
2022
medline:
18
5
2022
Statut:
epublish
Résumé
Complex-I-deficiency represents the most frequent pathogenetic cause of human mitochondriopathies. Therapeutic options for these neurodevelopmental life-threating disorders do not exist, partly due to the scarcity of appropriate model systems to study them. Caenorhabditis elegans is a genetically tractable model organism widely used to investigate neuronal pathologies. Here, we generate C. elegans models for mitochondriopathies and show that depletion of complex I subunits recapitulates biochemical, cellular and neurodevelopmental aspects of the human diseases. We exploit two models, nuo-5/NDUFS1- and lpd-5/NDUFS4-depleted animals, for a suppressor screening that identifies lutein for its ability to rescue animals' neurodevelopmental deficits. We uncover overexpression of synaptic neuroligin as an evolutionarily conserved consequence of mitochondrial dysfunction, which we find to mediate an early cholinergic defect in C. elegans. We show lutein exerts its beneficial effects by restoring neuroligin expression independently from its antioxidant activity, thus pointing to a possible novel pathogenetic target for the human disease.
Identifiants
pubmed: 35551180
doi: 10.1038/s41467-022-29972-4
pii: 10.1038/s41467-022-29972-4
pmc: PMC9098500
doi:
Substances chimiques
Caenorhabditis elegans Proteins
0
Lutein
X72A60C9MT
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2620Subventions
Organisme : NIEHS NIH HHS
ID : P42 ES010356
Pays : United States
Organisme : NIH HHS
ID : P40 OD010440
Pays : United States
Informations de copyright
© 2022. The Author(s).
Références
Kwong, J. Q., Beal, M. F. & Manfredi, G. The role of mitochondria in inherited neurodegenerative diseases. J. Neurochem. 97, 1659–75(2006).
pubmed: 16805775
doi: 10.1111/j.1471-4159.2006.03990.x
Distelmaier, F. et al. Mitochondrial complex I deficiency: from organelle dysfunction to clinical disease. Brain 132, 833–842 (2009).
pubmed: 19336460
doi: 10.1093/brain/awp058
Gorman, G. S. et al. Mitochondrial diseases. Nat. Rev. Dis. Prim. 2, 16080 (2016).
pubmed: 27775730
doi: 10.1038/nrdp.2016.80
Fiedorczuk, K. & Sazanov, L. A. Mammalian mitochondrial complex I structure and disease-causing mutations. Trends Cell Biol. 28, 835–867 (2018).
pubmed: 30055843
doi: 10.1016/j.tcb.2018.06.006
Baertling, F. et al. A guide to diagnosis and treatment of Leigh syndrome. J. Neurol. Neurosurg. Psychiatry 85, 257–265 (2014).
pubmed: 23772060
doi: 10.1136/jnnp-2012-304426
Silverman, G. A. et al. Modeling molecular and cellular aspects of human disease using the nematode Caenorhabditis elegans. Pediatr. Res. 65, 10–18 (2009).
pubmed: 18852689
pmcid: 2731241
doi: 10.1203/PDR.0b013e31819009b0
Ventura, N., Rea, S. L. & Testi, R. Long-lived C. elegans mitochondrial mutants as a model for human mitochondrial-associated diseases. Exp. Gerontol. 41, 974–991 (2006).
pubmed: 16945497
doi: 10.1016/j.exger.2006.06.060
O’Reilly, L. P. et al. C. elegans in high-throughput drug discovery. Adv. Drug Deliv. Rev. 69-70, 247–253 (2014).
pubmed: 24333896
doi: 10.1016/j.addr.2013.12.001
Artal-Sanz, M., de Jong, L. & Tavernarakis, N. Caenorhabditis elegans: a versatile platform for drug discovery. Biotechnol. J. 1, 1405–1418 (2006).
pubmed: 17109493
doi: 10.1002/biot.200600176
Maglioni, S., Arsalan, N. & Ventura, N. C. elegans screening strategies to identify pro-longevity interventions. Mech. Ageing Dev. 157, 60–69 (2016).
pubmed: 27473404
doi: 10.1016/j.mad.2016.07.010
Lublin, A. L. & Link, C. D. Alzheimer’s disease drug discovery: in vivo screening using Caenorhabditis elegans as a model for beta-amyloid peptide-induced toxicity. Drug Discov. Today Technol. 10, e115–e119 (2013).
pubmed: 24050239
doi: 10.1016/j.ddtec.2012.02.002
Alexander, A. G., Marfil, V. & Li, C. Use of Caenorhabditis elegans as a model to study Alzheimer’s disease and other neurodegenerative diseases. Front. Genet. 5, 279 (2014).
pubmed: 25250042
pmcid: 4155875
doi: 10.3389/fgene.2014.00279
Teschendorf, D. & Link, C. D. What have worm models told us about the mechanisms of neuronal dysfunction in human neurodegenerative diseases? Mol. Neurodegener. 4, 38 (2009).
pubmed: 19785750
pmcid: 2762972
doi: 10.1186/1750-1326-4-38
Helmcke, K. J., Avila, D. S. & Aschner, M. Utility of Caenorhabditis elegans in high throughput neurotoxicological research. Neurotoxicol. Teratol. 32, 62–67 (2010).
pubmed: 19087888
doi: 10.1016/j.ntt.2008.11.005
Maglioni, S. & Ventura, N. C. elegans as a model organism for human mitochondrial associated disorders. Mitochondrion. 30, 117–125 (2016).
pubmed: 26906059
doi: 10.1016/j.mito.2016.02.003
Polyak, E. et al. N-acetylcysteine and vitamin E rescue animal longevity and cellular oxidative stress in pre-clinical models of mitochondrial complex I disease. Mol. Genet. Metab. 123, 449–462 (2018).
pubmed: 29526616
pmcid: 5891356
doi: 10.1016/j.ymgme.2018.02.013
Ventura, N. & Rea, S. L. Caenorhabditis elegans mitochondrial mutants as an investigative tool to study human neurodegenerative diseases associated with mitochondrial dysfunction. Biotechnol. J. 2, 584–595 (2007).
pubmed: 17443764
doi: 10.1002/biot.200600248
Hartman, P. S. et al. Mitochondrial mutations differentially affect aging, mutability and anesthetic sensitivity in Caenorhabditis elegans. Mech. Ageing Dev. 122, 1187–1201 (2001).
pubmed: 11389932
doi: 10.1016/S0047-6374(01)00259-7
Rea, S. L., Ventura, N. & Johnson, T. E. Relationship between mitochondrial electron transport chain dysfunction, development, and life extension in Caenorhabditis elegans. PLoS Biol. 5, e259 (2007).
pubmed: 17914900
pmcid: 1994989
doi: 10.1371/journal.pbio.0050259
Ventura, N. et al. p53/CEP-1 increases or decreases lifespan, depending on level of mitochondrial bioenergetic stress. Aging Cell 8, 380–393 (2009).
pubmed: 19416129
doi: 10.1111/j.1474-9726.2009.00482.x
Maglioni, S. et al. Mitochondrial bioenergetic changes during development as an indicator of C. elegans health-span. Aging 11, 6535–6554 (2019).
pubmed: 31454791
pmcid: 6738431
doi: 10.18632/aging.102208
Tsang, W. Y. & Lemire, B. D. Mitochondrial genome content is regulated during nematode development. Biochem. Biophys. Res. Commun. 291, 8–16 (2002).
pubmed: 11829454
doi: 10.1006/bbrc.2002.6394
Ndegwa, S. & Lemire, B. D. Caenorhabditis elegans development requires mitochondrial function in the nervous system. Biochem. Biophys. Res. Commun. 319, 1307–1313 (2004).
pubmed: 15194510
doi: 10.1016/j.bbrc.2004.05.108
Maglioni, S. et al. Mitochondrial stress extends lifespan in C. elegans through neuronal hormesis. Exp. Gerontol. 56, 89–98 (2014).
pubmed: 24709340
doi: 10.1016/j.exger.2014.03.026
Gorman, G. S. et al. Perceived fatigue is highly prevalent and debilitating in patients with mitochondrial disease. Neuromuscul. Disord. 25, 563–566 (2015).
pubmed: 26031904
pmcid: 4502433
doi: 10.1016/j.nmd.2015.03.001
Matthies, D. S. et al. The Caenorhabditis elegans choline transporter CHO-1 sustains acetylcholine synthesis and motor function in an activity-dependent manner. J. Neurosci. 26, 6200–6212 (2006).
pubmed: 16763028
pmcid: 6675188
doi: 10.1523/JNEUROSCI.5036-05.2006
Gabaldon, T., Rainey, D. & Huynen, M. A. Tracing the evolution of a large protein complex in the eukaryotes, NADH:ubiquinone oxidoreductase (Complex I). J. Mol. Biol. 348, 857–870 (2005).
pubmed: 15843018
doi: 10.1016/j.jmb.2005.02.067
Ni, Y. et al. Mutations in NDUFS1 cause metabolic reprogramming and disruption of the electron transfer. Cells. 8, 1149 (2019).
pmcid: 6829531
doi: 10.3390/cells8101149
Ugalde, C. et al. Differences in assembly or stability of complex I and other mitochondrial OXPHOS complexes in inherited complex I deficiency. Hum. Mol. Genet. 13, 659–667 (2004).
pubmed: 14749350
doi: 10.1093/hmg/ddh071
Mango, S. E. The C. elegans pharynx: a model for organogenesis. (ed. WormBook), http://www.wormbook.org (The C. elegans Research Community, WormBook, 2007).
Brinkmann, V. et al. Dietary and environmental factors have opposite AhR-dependent effects on C. elegans healthspan. Aging 13, 104–133 (2020).
pubmed: 33349622
pmcid: 7835051
doi: 10.18632/aging.202316
Meyer, J. N. et al. Mitochondria as a target of environmental toxicants. Toxicol. Sci. 134, 1–17 (2013).
pubmed: 23629515
pmcid: 3693132
doi: 10.1093/toxsci/kft102
Meyer, J. N., Leuthner, T. C. & Luz, A. L. Mitochondrial fusion, fission, and mitochondrial toxicity. Toxicology 391, 42–53 (2017).
pubmed: 28789970
doi: 10.1016/j.tox.2017.07.019
Yoneda, T. et al. Compartment-specific perturbation of protein handling activates genes encoding mitochondrial chaperones. J. Cell Sci. 117, 4055–4066 (2004).
pubmed: 15280428
doi: 10.1242/jcs.01275
Schiavi, A. et al. Autophagy induction extends lifespan and reduces lipid content in response to frataxin silencing in C. elegans. Exp. Gerontol. 48, 191–201 (2013).
pubmed: 23247094
pmcid: 3572394
doi: 10.1016/j.exger.2012.12.002
Liu, Y. et al. Caenorhabditis elegans pathways that surveil and defend mitochondria. Nature 508, 406–410 (2014).
pubmed: 24695221
pmcid: 4102179
doi: 10.1038/nature13204
Lapierre, L. R. et al. The TFEB orthologue HLH-30 regulates autophagy and modulates longevity in Caenorhabditis elegans. Nat. Commun. 4, 2267 (2013).
pubmed: 23925298
doi: 10.1038/ncomms3267
Maglioni, S. et al. An automated phenotype-based microscopy screen to identify pro-longevity interventions acting through mitochondria in C. elegans. Biochim. Biophys. Acta 1847, 1469–1478 (2015).
pubmed: 25979236
doi: 10.1016/j.bbabio.2015.05.004
Britton, G., Liaaen-Jensen, S. & Pfander, H. Carotenoids. Volume 1B: Spectroscopy. Birkhäuser Verlag AG, Basel (1995). xvi + 360 pp.
Santocono, M. et al. Influence of astaxanthin, zeaxanthin and lutein on DNA damage and repair in UVA-irradiated cells. J. Photochem. Photobiol. B 85, 205–15. (2006).
pubmed: 16962787
doi: 10.1016/j.jphotobiol.2006.07.009
Swanson H. M., Smith J. R. Jr, Gong X., Rubin L. P. Lutein, but not other carotenoids, selectively inhibits breast cancer cell growth through several molecular mechanisms. FASEB J. 30, 34.2 (2016).
Liu, R. et al. Lutein and zeaxanthin supplementation and association with visual function in age-related macular degeneration. Investig. Ophthalmol. Vis. Sci. 56, 252–258 (2014).
doi: 10.1167/iovs.14-15553
Kiko, T. et al. Significance of lutein in red blood cells of Alzheimer’s disease patients. J. Alzheimers Dis. 28, 593–600 (2012).
pubmed: 22045492
doi: 10.3233/JAD-2011-111493
Sujak, A. et al. Lutein and zeaxanthin as protectors of lipid membranes against oxidative damage: the structural aspects. Arch. Biochem. Biophys. 371, 301–307 (1999).
pubmed: 10545218
doi: 10.1006/abbi.1999.1437
Cristina, D. et al. A regulated response to impaired respiration slows behavioral rates and increases lifespan in Caenorhabditis elegans. PLoS Genet. 5, e1000450 (2009).
pubmed: 19360127
pmcid: 2660839
doi: 10.1371/journal.pgen.1000450
Baruah, A. et al. CEP-1, the Caenorhabditis elegans p53 homolog, mediates opposing longevity outcomes in mitochondrial electron transport chain mutants. PLoS Genet. 10, e1004097 (2014).
pubmed: 24586177
pmcid: 3937132
doi: 10.1371/journal.pgen.1004097
Oh, K. H. & Kim H. Aldicarb-induced paralysis assay to determine defects in synaptic transmission in Caenorhabditis elegans. Bio Protoc. 7, e2400 (2017).
pubmed: 28868330
pmcid: 5580937
doi: 10.21769/BioProtoc.2400
Mahoney, T. R., Luo, S. & Nonet, M. L. Analysis of synaptic transmission in Caenorhabditis elegans using an aldicarb-sensitivity assay. Nat. Protoc. 1, 1772–1777 (2006).
pubmed: 17487159
doi: 10.1038/nprot.2006.281
Mulcahy, B., Holden-Dye, L. & O’Connor, V. Pharmacological assays reveal age-related changes in synaptic transmission at the Caenorhabditis elegans neuromuscular junction that are modified by reduced insulin signalling. J. Exp. Biol. 216, 492–501 (2013).
pubmed: 23038730
Locke, C. et al. Paradigms for pharmacological characterization of C. elegans synaptic transmission mutants. J. Vis. Exp. 18, 837 (2008).
Thapliyal, S. & Babu, K., Pentylenetetrazole (PTZ)-induced convulsion assay to determine GABAergic defects in Caenorhabditis elegans. Bio Protoc. 8, e2989 (2018).
pubmed: 30283811
pmcid: 6166856
doi: 10.21769/BioProtoc.2989
Fleming, J. T. et al. Caenorhabditis elegans levamisole resistance genes lev-1, unc-29, and unc-38 encode functional nicotinic acetylcholine receptor subunits. J. Neurosci. 17, 5843–5857 (1997).
pubmed: 9221782
pmcid: 6573193
doi: 10.1523/JNEUROSCI.17-15-05843.1997
Lemons, M. L. An inquiry-based approach to study the synapse: student-driven experiments using C. elegans. J. Undergrad. Neurosci. Educ. 15, A44–A55 (2016).
pubmed: 27980470
pmcid: 5105963
Weimer, R. M. et al. UNC-13 and UNC-10/rim localize synaptic vesicles to specific membrane domains. J. Neurosci. 26, 8040–8047 (2006).
pubmed: 16885217
pmcid: 3874421
doi: 10.1523/JNEUROSCI.2350-06.2006
Meissner, B. et al. Determining the sub-cellular localization of proteins within Caenorhabditis elegans body wall muscle. PLoS ONE 6, e19937 (2011).
pubmed: 21611156
pmcid: 3096668
doi: 10.1371/journal.pone.0019937
Sandoval, G. M. et al. A genetic interaction between the vesicular acetylcholine transporter VAChT/UNC-17 and synaptobrevin/SNB-1 in C. elegans. Nat. Neurosci. 9, 599–601 (2006).
pubmed: 16604067
doi: 10.1038/nn1685
Hu, Z. et al. Neurexin and neuroligin mediate retrograde synaptic inhibition in C. elegans. Science 337, 980–984 (2012).
pubmed: 22859820
pmcid: 3791080
doi: 10.1126/science.1224896
Staab, T. A. et al. Regulation of synaptic nlg-1/neuroligin abundance by the skn-1/Nrf stress response pathway protects against oxidative stress. PLoS Genet. 10, e1004100 (2014).
pubmed: 24453991
pmcid: 3894169
doi: 10.1371/journal.pgen.1004100
Calahorro, F. & Ruiz-Rubio, M. Functional phenotypic rescue of Caenorhabditis elegans neuroligin-deficient mutants by the human and rat NLGN1 genes. PLoS ONE 7, e39277 (2012).
pubmed: 22723984
pmcid: 3377638
doi: 10.1371/journal.pone.0039277
Silva-Pinheiro, P. et al. A single intravenous injection of AAV-PHP.B-hNDUFS4 ameliorates the phenotype of Ndufs4 (-/-) Mice. Mol. Ther. Methods Clin. Dev. 17, 1071–1078 (2020).
pubmed: 32478122
pmcid: 7248291
doi: 10.1016/j.omtm.2020.04.026
Dell’agnello, C. et al. Increased longevity and refractoriness to Ca(2+)-dependent neurodegeneration in Surf1 knockout mice. Hum. Mol. Genet. 16, 431–44. (2007).
pubmed: 17210671
doi: 10.1093/hmg/ddl477
Inak, G. et al. Defective metabolic programming impairs early neuronal morphogenesis in neural cultures and an organoid model of Leigh syndrome. Nat. Commun. 12, 1929 (2021).
pubmed: 33771987
pmcid: 7997884
doi: 10.1038/s41467-021-22117-z
Dillin, A. et al. Rates of behavior and aging specified by mitochondrial function during development. Science 298, 2398–401. (2002).
pubmed: 12471266
doi: 10.1126/science.1077780
Bennett, C. F. et al. Activation of the mitochondrial unfolded protein response does not predict longevity in Caenorhabditis elegans. Nat. Commun. 5, 3483 (2014).
pubmed: 24662282
doi: 10.1038/ncomms4483
Bjorkman, K. et al. Broad phenotypic variability in patients with complex I deficiency due to mutations in NDUFS1 and NDUFV1. Mitochondrion 21, 33–40 (2015).
pubmed: 25615419
doi: 10.1016/j.mito.2015.01.003
Luz, A. L. et al. Deficiencies in mitochondrial dynamics sensitize Caenorhabditis elegans to arsenite and other mitochondrial toxicants by reducing mitochondrial adaptability. Toxicology 387, 81–94 (2017).
pubmed: 28602540
doi: 10.1016/j.tox.2017.05.018
Muraresku, C. C., McCormick, E. M. & Falk, M. J. Mitochondrial disease: advances in clinical diagnosis, management, therapeutic development, and preventative strategies. Curr. Genet Med. Rep. 6, 62–72 (2018).
pubmed: 30393588
pmcid: 6208355
doi: 10.1007/s40142-018-0138-9
Devine, M. J. & Kittler, J. T. Mitochondria at the neuronal presynapse in health and disease. Nat. Rev. Neurosci. 19, 63–80 (2018).
pubmed: 29348666
doi: 10.1038/nrn.2017.170
Nikoletopoulou, V. & Tavernarakis, N. Regulation and roles of autophagy at synapses. Trends Cell Biol. 28, 646–661 (2018).
pubmed: 29731196
doi: 10.1016/j.tcb.2018.03.006
Schiavi, A. et al. Iron-starvation-induced mitophagy mediates lifespan extension upon mitochondrial stress in C. elegans. Curr. Biol. 25, 1810–1822 (2015).
pubmed: 26144971
doi: 10.1016/j.cub.2015.05.059
Matzinger, M., Fischhuber, K. & Heiss, E. H. Activation of Nrf2 signaling by natural products-can it alleviate diabetes? Biotechnol. Adv. 36, 1738–1767 (2018).
pubmed: 29289692
doi: 10.1016/j.biotechadv.2017.12.015
Hunter, J. W. et al. Neuroligin-deficient mutants of C. elegans have sensory processing deficits and are hypersensitive to oxidative stress and mercury toxicity. Dis. Model Mech. 3, 366–376 (2010).
pubmed: 20083577
pmcid: 4068633
doi: 10.1242/dmm.003442
Grella Miranda, C. et al. Influence of nanoencapsulated lutein on acetylcholinesterase activity: In vitro determination, kinetic parameters, and in silico docking simulations. Food Chem. 307, 125523 (2020).
pubmed: 31639572
doi: 10.1016/j.foodchem.2019.125523
Nolan, J. M. et al. The impact of supplemental macular carotenoids in Alzheimer’s disease: a randomized clinical trial. J. Alzheimers Dis. 44, 1157–1169 (2015).
pubmed: 25408222
doi: 10.3233/JAD-142265
Desmidt, T., Hommet, C. & Camus, V. Pharmacological treatments of behavioral and psychological symptoms of dementia in Alzheimer’s disease: role of acetylcholinesterase inhibitors and memantine. Geriatr. Psychol. Neuropsychiatr. Vieil. 14, 300–306 (2016).
pubmed: 27651011
Dufort-Gervais, J. et al. Neuroligin-1 is altered in the hippocampus of Alzheimer’s disease patients and mouse models, and modulates the toxicity of amyloid-beta oligomers. Sci. Rep. 10, 6956 (2020).
pubmed: 32332783
pmcid: 7181681
doi: 10.1038/s41598-020-63255-6
Xue, C. et al. Management of ocular diseases using lutein and zeaxanthin: what have we learned from experimental animal studies? J. Ophthalmol. 2015, 523027 (2015).
pubmed: 26617995
pmcid: 4651639
Nataraj, J. et al. Lutein protects dopaminergic neurons against MPTP-induced apoptotic death and motor dysfunction by ameliorating mitochondrial disruption and oxidative stress. Nutr. Neurosci. 19, 237–246 (2016).
pubmed: 25730317
doi: 10.1179/1476830515Y.0000000010
Arunkumar, R. et al. Biodegradable poly (lactic-co-glycolic acid)-polyethylene glycol nanocapsules: an efficient carrier for improved solubility, bioavailability, and anticancer property of lutein. J. Pharm. Sci. 104, 2085–2093 (2015).
pubmed: 25824524
doi: 10.1002/jps.24436
Kamil, A. et al. Bioavailability and biodistribution of nanodelivered lutein. Food Chem. 192, 915–923 (2016).
pubmed: 26304429
doi: 10.1016/j.foodchem.2015.07.106
Andreux, P. A. et al. A method to identify and validate mitochondrial modulators using mammalian cells and the worm C. elegans. Sci. Rep. 4, 5285 (2014).
pubmed: 24923838
pmcid: 4055904
doi: 10.1038/srep05285
Andreux, P. A., Houtkooper, R. H. & Auwerx, J. Pharmacological approaches to restore mitochondrial function. Nat. Rev. Drug Discov. 12, 465–483 (2013).
pubmed: 23666487
pmcid: 3896945
doi: 10.1038/nrd4023
Jansen-Olesen, I., Tfelt-Hansen, P. & Olesen, J. Animal migraine models for drug development: status and future perspectives. CNS Drugs 27, 1049–68. (2013).
pubmed: 24234657
doi: 10.1007/s40263-013-0121-7
Kamath, R. S. & Ahringer, J. Genome-wide RNAi screening in Caenorhabditis elegans. Methods 30, 313–321 (2003).
pubmed: 12828945
doi: 10.1016/S1046-2023(03)00050-1
Pierce-Shimomura, J. T. et al. Genetic analysis of crawling and swimming locomotory patterns in C. elegans. Proc. Natl Acad. Sci. USA 105, 20982–20987 (2008).
pubmed: 19074276
pmcid: 2634943
doi: 10.1073/pnas.0810359105
Lockery, S. R. et al. A microfluidic device for whole-animal drug screening using electrophysiological measures in the nematode C. elegans. Lab Chip 12, 2211–2220 (2012).
pubmed: 22588281
pmcid: 3372093
doi: 10.1039/c2lc00001f
Dabbish, N. S. & Raizen, D. M. GABAergic synaptic plasticity during a developmentally regulated sleep-like state in C. elegans. J. Neurosci. 31, 15932–15943 (2011).
pubmed: 22049436
pmcid: 3226813
doi: 10.1523/JNEUROSCI.0742-11.2011
Luz, A. L. et al. In vivo determination of mitochondrial function using luciferase-expressing Caenorhabditis elegans: contribution of oxidative phosphorylation, glycolysis, and fatty acid oxidation to toxicant-induced dysfunction. Curr. Protoc. Toxicol. 69, 25.8.1–25.8.22 (2016).
doi: 10.1002/cptx.10
Meyer, J. N. QPCR: a tool for analysis of mitochondrial and nuclear DNA damage in ecotoxicology. Ecotoxicology 19, 804–811 (2010).
pubmed: 20049526
pmcid: 2844971
doi: 10.1007/s10646-009-0457-4
Carvalho, B. S. & Irizarry, R. A. A framework for oligonucleotide microarray preprocessing. Bioinformatics 26, 2363–2367 (2010).
pubmed: 20688976
pmcid: 2944196
doi: 10.1093/bioinformatics/btq431
Ritchie, M. E. et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 43, e47 (2015).
pubmed: 25605792
pmcid: 4402510
doi: 10.1093/nar/gkv007
Bindea, G., Galon, J. & Mlecnik, B. CluePedia Cytoscape plugin: pathway insights using integrated experimental and in silico data. Bioinformatics 29, 661–663 (2013).
pubmed: 23325622
pmcid: 3582273
doi: 10.1093/bioinformatics/btt019
Yu, G. enrichplot: Visualization of Functional Enrichment Result. (R package version 1.0.2. Bioconductor, 2018).
Team, R. C. R: A Language and Environment for Statistical Computing. (R Foundation for Statistical Computing, Vienna, Austria, 2018).
Bassan, P. et al. Resonant Mie scattering (RMieS) correction of infrared spectra from highly scattering biological samples. Analyst 135, 268–277 (2010).
pubmed: 20098758
doi: 10.1039/B921056C
Kruse, S. E. et al. Mice with mitochondrial complex I deficiency develop a fatal encephalomyopathy. Cell Metab. 7, 312–320 (2008).
pubmed: 18396137
pmcid: 2593686
doi: 10.1016/j.cmet.2008.02.004
Fernandez-Mosquera, L. et al. Mitochondrial respiratory chain deficiency inhibits lysosomal hydrolysis. Autophagy 15, 1572–1591 (2019).
pubmed: 30917721
pmcid: 6693470
doi: 10.1080/15548627.2019.1586256
Distelmaier, F. et al. Mitochondrial dysfunction in primary human fibroblasts triggers an adaptive cell survival program that requires AMPK-alpha. Biochim. Biophys. Acta 1852, 529–540 (2015).
pubmed: 25536029
doi: 10.1016/j.bbadis.2014.12.012