OXR1 maintains the retromer to delay brain aging under dietary restriction.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
11 Jan 2024
11 Jan 2024
Historique:
received:
02
08
2023
accepted:
07
12
2023
medline:
12
1
2024
pubmed:
12
1
2024
entrez:
11
1
2024
Statut:
epublish
Résumé
Dietary restriction (DR) delays aging, but the mechanism remains unclear. We identified polymorphisms in mtd, the fly homolog of OXR1, which influenced lifespan and mtd expression in response to DR. Knockdown in adulthood inhibited DR-mediated lifespan extension in female flies. We found that mtd/OXR1 expression declines with age and it interacts with the retromer, which regulates trafficking of proteins and lipids. Loss of mtd/OXR1 destabilized the retromer, causing improper protein trafficking and endolysosomal defects. Overexpression of retromer genes or pharmacological restabilization with R55 rescued lifespan and neurodegeneration in mtd-deficient flies and endolysosomal defects in fibroblasts from patients with lethal loss-of-function of OXR1 variants. Multi-omic analyses in flies and humans showed that decreased Mtd/OXR1 is associated with aging and neurological diseases. mtd/OXR1 overexpression rescued age-related visual decline and tauopathy in a fly model. Hence, OXR1 plays a conserved role in preserving retromer function and is critical for neuronal health and longevity.
Identifiants
pubmed: 38212606
doi: 10.1038/s41467-023-44343-3
pii: 10.1038/s41467-023-44343-3
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
467Subventions
Organisme : U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)
ID : R01AG061165
Organisme : U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)
ID : R56AG070705-01
Organisme : U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)
ID : T32AG000266
Organisme : U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)
ID : 5F31AG062112
Organisme : U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)
ID : R01AG07326
Organisme : U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)
ID : U01AG072439
Organisme : U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)
ID : R56AG070705
Organisme : Larry L. Hillblom Foundation (Larry L. Hillblom Foundation, Inc.)
ID : 2019-A-026-FEL
Organisme : U.S. Department of Health & Human Services | NIH | National Center for Research Resources (NCRR)
ID : 1S10 OD028654
Informations de copyright
© 2024. The Author(s).
Références
Mattson, M. P. Gene-diet interactions in brain aging and neurodegenerative disorders. Ann. Intern. Med. 139, 441–444 (2003).
pubmed: 12965973
doi: 10.7326/0003-4819-139-5_Part_2-200309021-00012
Wilson, K. A. et al. Evaluating the beneficial effects of dietary restrictions: A framework for precision nutrigeroscience. Cell Metab. 33, 2142–2173 (2021).
pubmed: 34555343
pmcid: 8845500
doi: 10.1016/j.cmet.2021.08.018
Mackay, T. F. et al. The Drosophila melanogaster Genetic Reference Panel. Nature 482, 173–178 (2012).
pubmed: 22318601
pmcid: 3683990
doi: 10.1038/nature10811
Wilson, K. A. et al. GWAS for Lifespan and Decline in Climbing Ability in Flies upon Dietary Restriction Reveal decima as a Mediator of Insulin-like Peptide Production. Curr. Biol. 30, 2749–2760 e2743 (2020).
pubmed: 32502405
pmcid: 7375902
doi: 10.1016/j.cub.2020.05.020
Wang, J. et al. Loss of Oxidation Resistance 1, OXR1, Is Associated with an Autosomal-Recessive Neurological Disease with Cerebellar Atrophy and Lysosomal Dysfunction. Am. J. Hum. Genet. 105, 1237–1253 (2019).
pubmed: 31785787
pmcid: 6904826
doi: 10.1016/j.ajhg.2019.11.002
Liu, K. X. et al. Neuron-specific antioxidant OXR1 extends survival of a mouse model of amyotrophic lateral sclerosis. Brain 138, 1167–1181 (2015).
pubmed: 25753484
pmcid: 4407188
doi: 10.1093/brain/awv039
Small, S. A. & Petsko, G. A. Retromer in Alzheimer disease, Parkinson disease and other neurological disorders. Nat. Rev. Neurosci. 16, 126–132 (2015).
pubmed: 25669742
doi: 10.1038/nrn3896
Gallon, M. & Cullen, P. J. Retromer and sorting nexins in endosomal sorting. Biochem. Soc. Trans. 43, 33–47 (2015).
pubmed: 25619244
doi: 10.1042/BST20140290
Volkert, M. R., Elliott, N. A. & Housman, D. E. Functional genomics reveals a family of eukaryotic oxidation protection genes. Proc. Natl. Acad. Sci. USA 97, 14530–14535 (2000).
pubmed: 11114193
pmcid: 18953
doi: 10.1073/pnas.260495897
Xu, H. et al. Zebrafish Oxr1a Knockout Reveals Its Role in Regulating Antioxidant Defenses and Aging. Genes (Basel) 11, 1118 (2020).
Finelli, M. J., Sanchez-Pulido, L., Liu, K. X., Davies, K. E. & Oliver, P. L. The Evolutionarily Conserved Tre2/Bub2/Cdc16 (TBC), Lysin Motif (LysM), Domain Catalytic (TLDc) Domain Is Neuroprotective against Oxidative Stress. J. Biol. Chem. 291, 2751–2763 (2016).
pubmed: 26668325
doi: 10.1074/jbc.M115.685222
Slattery, M. et al. Diverse patterns of genomic targeting by transcriptional regulators in Drosophila melanogaster. Genome Res. 24, 1224–1235 (2014).
pubmed: 24985916
pmcid: 4079976
doi: 10.1101/gr.168807.113
Negre, N. et al. A cis-regulatory map of the Drosophila genome. Nature 471, 527–531 (2011).
pubmed: 21430782
pmcid: 3179250
doi: 10.1038/nature09990
Lachmann, A. et al. Massive mining of publicly available RNA-seq data from human and mouse. Nat. Commun. 9, 1366 (2018).
pubmed: 29636450
pmcid: 5893633
doi: 10.1038/s41467-018-03751-6
Maruzs, T. et al. Retromer Ensures the Degradation of Autophagic Cargo by Maintaining Lysosome Function in Drosophila. Traffic 16, 1088–1107 (2015).
pubmed: 26172538
doi: 10.1111/tra.12309
Cui, Y. et al. Retromer has a selective function in cargo sorting via endosome transport carriers. J. Cell Biol. 218, 615–631 (2019).
pubmed: 30559172
pmcid: 6363445
doi: 10.1083/jcb.201806153
Lin, G. et al. Phospholipase PLA2G6, a Parkinsonism-Associated Gene, Affects Vps26 and Vps35, Retromer Function, and Ceramide Levels, Similar to alpha-Synuclein Gain. Cell Metab. 28, 605–618 e606 (2018).
pubmed: 29909971
doi: 10.1016/j.cmet.2018.05.019
Lane, R. F. et al. Vps10 family proteins and the retromer complex in aging-related neurodegeneration and diabetes. J. Neurosci. 32, 14080–14086 (2012).
pubmed: 23055476
pmcid: 3576841
doi: 10.1523/JNEUROSCI.3359-12.2012
Wilson, K. A. The understudied links of the retromer complex to age-related pathways. Geroscience 44, 19–24 (2022).
pubmed: 34370162
doi: 10.1007/s11357-021-00430-1
Vagnozzi, A. N. & Pratico, D. Endosomal sorting and trafficking, the retromer complex and neurodegeneration. Mol. Psychiatry 24, 857–868 (2019).
pubmed: 30120416
doi: 10.1038/s41380-018-0221-3
Mecozzi, V. J. et al. Pharmacological chaperones stabilize retromer to limit APP processing. Nat. Chem. Biol. 10, 443–449 (2014).
pubmed: 24747528
pmcid: 4076047
doi: 10.1038/nchembio.1508
Yoshii, S. R. & Mizushima, N. Monitoring and Measuring Autophagy. Int J Mol Sci. 18, 1865 (2017).
Wang, S. et al. The retromer complex is required for rhodopsin recycling and its loss leads to photoreceptor degeneration. PLoS Biol. 12, e1001847 (2014).
pubmed: 24781186
pmcid: 4004542
doi: 10.1371/journal.pbio.1001847
Kusne, Y., Wolf, A. B., Townley, K., Conway, M. & Peyman, G. A. Visual system manifestations of Alzheimer’s disease. Acta. Ophthalmol. 95, e668–e676 (2017).
pubmed: 27864881
doi: 10.1111/aos.13319
Roberts, R. O. et al. Association Between Olfactory Dysfunction and Amnestic Mild Cognitive Impairment and Alzheimer Disease Dementia. JAMA Neurol. 73, 93–101 (2016).
pubmed: 26569387
pmcid: 4710557
doi: 10.1001/jamaneurol.2015.2952
Bruderer, R. et al. Optimization of Experimental Parameters in Data-Independent Mass Spectrometry Significantly Increases Depth and Reproducibility of Results. Mol. Cell. Proteom.: MCP 16, 2296–2309 (2017).
pubmed: 29070702
doi: 10.1074/mcp.RA117.000314
Johnson, E. C. B. et al. Large-scale deep multi-layer analysis of Alzheimer’s disease brain reveals strong proteomic disease-related changes not observed at the RNA level. Nat. Neurosci. 25, 213–225 (2022).
pubmed: 35115731
pmcid: 8825285
doi: 10.1038/s41593-021-00999-y
Jia, K., Cui, C., Gao, Y., Zhou, Y. & Cui, Q. An analysis of aging-related genes derived from the Genotype-Tissue Expression project (GTEx). Cell Death Discov. 4, 26 (2018).
pubmed: 30155276
doi: 10.1038/s41420-018-0093-y
Mele, M. et al. Human genomics. The human transcriptome across tissues and individuals. Science 348, 660–665 (2015).
pubmed: 25954002
pmcid: 4547472
doi: 10.1126/science.aaa0355
Chen, E. Y. et al. Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool. BMC Bioinformatics 14, 128 (2013).
pubmed: 23586463
pmcid: 3637064
doi: 10.1186/1471-2105-14-128
Simoes, S. et al. Tau and other proteins found in Alzheimer’s disease spinal fluid are linked to retromer-mediated endosomal traffic in mice and humans. Sci. Trans. Med. 12, eaba6334 (2020).
Qureshi, Y. H. et al. The neuronal retromer can regulate both neuronal and microglial phenotypes of Alzheimer’s disease. Cell Rep 38, 110262 (2022).
pubmed: 35045281
pmcid: 8830374
doi: 10.1016/j.celrep.2021.110262
Simoes, S. et al. Alzheimer’s vulnerable brain region relies on a distinct retromer core dedicated to endosomal recycling. Cell Rep. 37, 110182 (2021).
pubmed: 34965419
pmcid: 8792909
doi: 10.1016/j.celrep.2021.110182
Moulton, M. J. et al. Neuronal ROS-induced glial lipid droplet formation is altered by loss of Alzheimer’s disease-associated genes. Proc. Natl. Acad. Sci. USA. 118, e2112095118 (2021).
Asadzadeh, J. et al. Retromer deficiency in Tauopathy models enhances the truncation and toxicity of Tau. Nat. Commun. 13, 5049 (2022).
pubmed: 36030267
pmcid: 9420134
doi: 10.1038/s41467-022-32683-5
Ye, H. et al. Retromer subunit, VPS29, regulates synaptic transmission and is required for endolysosomal function in the aging brain. Elife 9, e51977 (2020).
Johnson, E. C. B. et al. Large-scale proteomic analysis of Alzheimer’s disease brain and cerebrospinal fluid reveals early changes in energy metabolism associated with microglia and astrocyte activation. Nat. Med. 26, 769–780 (2020).
pubmed: 32284590
pmcid: 7405761
doi: 10.1038/s41591-020-0815-6
Katewa, S. D. et al. Intramyocellular fatty-acid metabolism plays a critical role in mediating responses to dietary restriction in Drosophila melanogaster. Cell Metab. 16, 97–103 (2012).
pubmed: 22768842
pmcid: 3400463
doi: 10.1016/j.cmet.2012.06.005
Morabito, M. V. et al. Hyperleucinemia causes hippocampal retromer deficiency linking diabetes to Alzheimer’s disease. Neurobiol. Dis. 65, 188–192 (2014).
pubmed: 24440570
pmcid: 4235335
doi: 10.1016/j.nbd.2013.12.017
Chae, C. W. et al. High glucose-mediated VPS26a down-regulation dysregulates neuronal amyloid precursor protein processing and tau phosphorylation. Br. J. Pharmacol. 179, 3934–3950 (2022).
pubmed: 35297035
doi: 10.1111/bph.15836
Knupp, A. et al. Depletion of the AD Risk Gene SORL1 Selectively Impairs Neuronal Endosomal Traffic Independent of Amyloidogenic APP Processing. Cell Rep 31, 107719 (2020).
pubmed: 32492427
pmcid: 7409533
doi: 10.1016/j.celrep.2020.107719
Pandey, S., Dhusia, K., Katara, P., Singh, S. & Gautam, B. An in silico analysis of deleterious single nucleotide polymorphisms and molecular dynamics simulation of disease linked mutations in genes responsible for neurodegenerative disorder. J. Biomol. Struct. Dyn. 38, 4259–4272 (2020).
Li, J. G., Chiu, J., Ramanjulu, M., Blass, B. E. & Pratico, D. A pharmacological chaperone improves memory by reducing Abeta and tau neuropathology in a mouse model with plaques and tangles. Mol. Neurodegeneration 15, 1 (2020).
doi: 10.1186/s13024-019-0350-4
Muhammad, A. et al. Retromer deficiency observed in Alzheimer’s disease causes hippocampal dysfunction, neurodegeneration, and Abeta accumulation. Proc. Natl. Acad. Sci. USA 105, 7327–7332 (2008).
pubmed: 18480253
pmcid: 2386077
doi: 10.1073/pnas.0802545105
Mir, R. et al. The Parkinson’s disease VPS35[D620N] mutation enhances LRRK2-mediated Rab protein phosphorylation in mouse and human. Biochem. J. 475, 1861–1883 (2018).
pubmed: 29743203
doi: 10.1042/BCJ20180248
Chen, X. et al. Parkinson’s disease-linked D620N VPS35 knockin mice manifest tau neuropathology and dopaminergic neurodegeneration. Proc. Natl. Acad. Sci. USA. 116, 5765–5774 (2019).
pubmed: 30842285
pmcid: 6431187
doi: 10.1073/pnas.1814909116
Zhao, Y. et al. Reduced LRRK2 in association with retromer dysfunction in post-mortem brain tissue from LRRK2 mutation carriers. Brain 141, 486–495 (2018).
pubmed: 29253086
doi: 10.1093/brain/awx344
Finan, G. M., Okada, H. & Kim, T. W. BACE1 retrograde trafficking is uniquely regulated by the cytoplasmic domain of sortilin. J. Biol. Chem. 286, 12602–12616 (2011).
pubmed: 21245145
pmcid: 3069461
doi: 10.1074/jbc.M110.170217
Cadby, G. et al. Comprehensive genetic analysis of the human lipidome identifies loci associated with lipid homeostasis with links to coronary artery disease. Nat. Commun. 13, 3124 (2022).
pubmed: 35668104
pmcid: 9170690
doi: 10.1038/s41467-022-30875-7
Nelson, C. S. et al. Cross-phenotype association tests uncover genes mediating nutrient response in Drosophila. BMC Genom. 17, 867 (2016).
doi: 10.1186/s12864-016-3137-9
Virtanen, P. et al. SciPy 1.0: fundamental algorithms for scientific computing in Python. Nat. Methods 17, 261–272 (2020).
pubmed: 32015543
pmcid: 7056644
doi: 10.1038/s41592-019-0686-2
David, L. A. et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature 505, 559–563 (2014).
pubmed: 24336217
doi: 10.1038/nature12820
Kulahoglu, C. & Brautigam, A. Quantitative transcriptome analysis using RNA-seq. Methods Mol. Biol. 1158, 71–91 (2014).
pubmed: 24792045
doi: 10.1007/978-1-4939-0700-7_5
Cook, K. R., Parks, A. L., Jacobus, L. M., Kaufman, T. C. & Matthews, K. A. New research resources at the Bloomington Drosophila Stock Center. Fly (Austin) 4, 88–91 (2010).
pubmed: 20160480
doi: 10.4161/fly.4.1.11230
Vissers, J. H., Manning, S. A., Kulkarni, A. & Harvey, K. F. A Drosophila RNAi library modulates Hippo pathway-dependent tissue growth. Nat. Commun. 7, 10368 (2016).
pubmed: 26758424
pmcid: 4735554
doi: 10.1038/ncomms10368
Bischof, J., Sheils, E. M., Bjorklund, M. & Basler, K. Generation of a transgenic ORFeome library in Drosophila. Nat. Protocols 9, 1607–1620 (2014).
pubmed: 24922270
doi: 10.1038/nprot.2014.105
Zid, B. M. et al. 4E-BP extends lifespan upon dietary restriction by enhancing mitochondrial activity in Drosophila. Cell 139, 149–160 (2009).
pubmed: 19804760
pmcid: 2759400
doi: 10.1016/j.cell.2009.07.034
Katewa, S. D. et al. Peripheral Circadian Clocks Mediate Dietary Restriction-Dependent Changes in Lifespan and Fat Metabolism in Drosophila. Cell Metab. 23, 143–154 (2016).
pubmed: 26626459
doi: 10.1016/j.cmet.2015.10.014
Osterwalder, T., Yoon, K. S., White, B. H. & Keshishian, H. A conditional tissue-specific transgene expression system using inducible GAL4. Proc. Natl. Acad. Sci. USA 98, 12596–12601 (2001).
pubmed: 11675495
pmcid: 60099
doi: 10.1073/pnas.221303298
Arya, G. H. et al. The genetic basis for variation in olfactory behavior in Drosophila melanogaster. Chem. Senses 40, 233–243 (2015).
pubmed: 25687947
pmcid: 4398050
doi: 10.1093/chemse/bjv001
Iyer, J. et al. Quantitative Assessment of Eye Phenotypes for Functional Genetic Studies Using Drosophila melanogaster. G3 6, 1427–1437 (2016).
pubmed: 26994292
pmcid: 4856093
doi: 10.1534/g3.116.027060
Escher, C. et al. Using iRT, a normalized retention time for more targeted measurement of peptides. Proteomics 12, 1111–1121 (2012).
pubmed: 22577012
pmcid: 3918884
doi: 10.1002/pmic.201100463
Gillet, L. C. et al. Targeted data extraction of the MS/MS spectra generated by data-independent acquisition: a new concept for consistent and accurate proteome analysis. Mol. Cell. Proteom.: MCP 11, O111 016717 (2012).
pubmed: 22261725
doi: 10.1074/mcp.O111.016717
Collins, B. C. et al. Multi-laboratory assessment of reproducibility, qualitative and quantitative performance of SWATH-mass spectrometry. Nat. Commun. 8, 291 (2017).
pubmed: 28827567
pmcid: 5566333
doi: 10.1038/s41467-017-00249-5
Burger, T. Gentle Introduction to the Statistical Foundations of False Discovery Rate in Quantitative Proteomics. J. Proteome Res. 17, 12–22 (2018).
pubmed: 29067805
doi: 10.1021/acs.jproteome.7b00170
Hou, J. et al. The Prognostic Value and the Oncogenic and Immunological Roles of Vacuolar Protein Sorting Associated Protein 26 A in Pancreatic Adenocarcinoma. Int. J. Mol. Sci. 24, 3486 (2023).