دورية أكاديمية
أعرض في EDS

ABCA7 deficiency causes neuronal dysregulation by altering mitochondrial lipid metabolism.

التفاصيل البيبلوغرافية
العنوان: ABCA7 deficiency causes neuronal dysregulation by altering mitochondrial lipid metabolism.
المؤلفون: Kawatani K; Department of Neuroscience, Mayo Clinic, Jacksonville, FL, 32224, USA., Holm ML; Department of Neuroscience, Mayo Clinic, Jacksonville, FL, 32224, USA., Starling SC; Department of Neuroscience, Mayo Clinic, Jacksonville, FL, 32224, USA., Martens YA; Department of Neuroscience, Mayo Clinic, Jacksonville, FL, 32224, USA.; SciNeuro Pharmaceuticals, Rockville, MD, 20850, USA., Zhao J; Department of Neuroscience, Mayo Clinic, Jacksonville, FL, 32224, USA.; Center for Regenerative Biotherapeutics, Mayo Clinic, Jacksonville, FL, 32224, USA., Lu W; Department of Neuroscience, Mayo Clinic, Jacksonville, FL, 32224, USA.; Center for Regenerative Biotherapeutics, Mayo Clinic, Jacksonville, FL, 32224, USA., Ren Y; Quantitative Health Sciences, Mayo Clinic, Jacksonville, FL, 32224, USA., Li Z; Department of Neuroscience, Mayo Clinic, Jacksonville, FL, 32224, USA., Jiang P; Department of Neuroscience, Mayo Clinic, Jacksonville, FL, 32224, USA., Jiang Y; Department of Neuroscience, Mayo Clinic, Jacksonville, FL, 32224, USA., Baker SK; Department of Neuroscience, Mayo Clinic, Jacksonville, FL, 32224, USA., Wang N; Department of Neuroscience, Mayo Clinic, Jacksonville, FL, 32224, USA., Roy B; Department of Neuroscience, Mayo Clinic, Jacksonville, FL, 32224, USA., Parsons TM; Department of Neuroscience, Mayo Clinic, Jacksonville, FL, 32224, USA.; Center for Regenerative Biotherapeutics, Mayo Clinic, Jacksonville, FL, 32224, USA., Perkerson RB 3rd; Center for Regenerative Biotherapeutics, Mayo Clinic, Jacksonville, FL, 32224, USA., Bao H; Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA., Han X; Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA., Bu G; Department of Neuroscience, Mayo Clinic, Jacksonville, FL, 32224, USA.; Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China., Kanekiyo T; Department of Neuroscience, Mayo Clinic, Jacksonville, FL, 32224, USA. kanekiyo.takahisa@mayo.edu.; Center for Regenerative Biotherapeutics, Mayo Clinic, Jacksonville, FL, 32224, USA. kanekiyo.takahisa@mayo.edu.
المصدر: Molecular psychiatry [Mol Psychiatry] 2024 Mar; Vol. 29 (3), pp. 809-819. Date of Electronic Publication: 2023 Dec 22.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Specialist Journals Country of Publication: England NLM ID: 9607835 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5578 (Electronic) Linking ISSN: 13594184 NLM ISO Abbreviation: Mol Psychiatry Subsets: MEDLINE
أسماء مطبوعة: Publication: 2000- : Houndmills, Basingstoke, UK : Nature Publishing Group Specialist Journals
Original Publication: Houndmills, Hampshire, UK ; New York, NY : Stockton Press, c1996-
مواضيع طبية MeSH: Mitochondria*/metabolism , Neurons*/metabolism , Lipid Metabolism*/physiology , Mice, Knockout* , Induced Pluripotent Stem Cells*/metabolism , ATP-Binding Cassette Transporters*/metabolism , ATP-Binding Cassette Transporters*/genetics, Humans ; Animals ; Mice ; Alzheimer Disease/metabolism ; Alzheimer Disease/pathology ; Alzheimer Disease/genetics ; Brain/metabolism
مستخلص: ABCA7 loss-of-function variants are associated with increased risk of Alzheimer's disease (AD). Using ABCA7 knockout human iPSC models generated with CRISPR/Cas9, we investigated the impacts of ABCA7 deficiency on neuronal metabolism and function. Lipidomics revealed that mitochondria-related phospholipids, such as phosphatidylglycerol and cardiolipin were reduced in the ABCA7-deficient iPSC-derived cortical organoids. Consistently, ABCA7 deficiency-induced alterations of mitochondrial morphology accompanied by reduced ATP synthase activity and exacerbated oxidative damage in the organoids. Furthermore, ABCA7-deficient iPSC-derived neurons showed compromised mitochondrial respiration and excess ROS generation, as well as enlarged mitochondrial morphology compared to the isogenic controls. ABCA7 deficiency also decreased spontaneous synaptic firing and network formation in iPSC-derived neurons, in which the effects were rescued by supplementation with phosphatidylglycerol or NAD + precursor, nicotinamide mononucleotide. Importantly, effects of ABCA7 deficiency on mitochondria morphology and synapses were recapitulated in synaptosomes isolated from the brain of neuron-specific Abca7 knockout mice. Together, our results provide evidence that ABCA7 loss-of-function contributes to AD risk by modulating mitochondria lipid metabolism.
(© 2023. The Author(s).)
References: Front Endocrinol (Lausanne). 2018 May 04;9:221. (PMID: 29780359)
Nat Genet. 2011 May;43(5):429-35. (PMID: 21460840)
Biology (Basel). 2022 Feb 16;11(2):. (PMID: 35205182)
Cells. 2021 Aug 24;10(9):. (PMID: 34571826)
J Neurophysiol. 1985 Apr;53(4):926-39. (PMID: 3998798)
Biochem Biophys Res Commun. 2003 Nov 14;311(2):313-8. (PMID: 14592415)
Biol Psychiatry. 2015 Jan 1;77(1):43-51. (PMID: 24951455)
Molecules. 2020 Dec 08;25(24):. (PMID: 33302541)
Trends Endocrinol Metab. 2012 Sep;23(9):420-8. (PMID: 22819213)
Prog Lipid Res. 2016 Jan;61:83-108. (PMID: 26703190)
Toxicol Lett. 2003 Apr 4;139(2-3):125-33. (PMID: 12628748)
BMC Neurol. 2015 Mar 01;15:19. (PMID: 25884176)
Nat Genet. 2022 Apr;54(4):412-436. (PMID: 35379992)
EMBO J. 2010 Jun 16;29(12):1976-87. (PMID: 20485265)
Anal Chem. 2009 Jun 1;81(11):4356-68. (PMID: 19408941)
Nat Genet. 2011 May;43(5):436-41. (PMID: 21460841)
PLoS One. 2019 Jul 29;14(7):e0219592. (PMID: 31356639)
Sci Rep. 2018 Mar 20;8(1):4919. (PMID: 29559686)
Mol Psychiatry. 2020 Jan;25(1):148-167. (PMID: 31391546)
Genomics. 2014 Feb-Mar;103(2-3):183-8. (PMID: 24345642)
BMC Bioinformatics. 2014 Jun 27;15:224. (PMID: 24972667)
J Cell Physiol. 2017 Mar;232(3):477-481. (PMID: 27442611)
Aging (Albany NY). 2020 Aug 27;12(16):16647-16662. (PMID: 32853175)
Science. 2017 May 26;356(6340):. (PMID: 28495876)
NPJ Aging Mech Dis. 2018 Nov 8;4:10. (PMID: 30416740)
Bioinformatics. 2014 Feb 15;30(4):523-30. (PMID: 24336805)
Neurol Genet. 2016 May 17;2(3):e79. (PMID: 27231719)
Sci Transl Med. 2018 Sep 19;10(459):. (PMID: 30232227)
Ageing Res Rev. 2022 Nov;81:101723. (PMID: 36038112)
Methods Mol Biol. 2014;1198:203-20. (PMID: 25270931)
Am J Physiol Regul Integr Comp Physiol. 2013 Mar 15;304(6):R393-406. (PMID: 23364527)
Genesis. 2001 Sep;31(1):37-42. (PMID: 11668676)
FEBS Lett. 2018 Apr;592(8):1273-1290. (PMID: 29067684)
Rapid Commun Mass Spectrom. 2008 Jul;22(13):2115-24. (PMID: 18523984)
Front Aging Neurosci. 2021 Feb 18;13:617588. (PMID: 33679375)
Nat Commun. 2020 Nov 2;11(1):5540. (PMID: 33139712)
Brain Res. 2016 Jul 15;1643:1-9. (PMID: 27130898)
Acta Neuropathol. 2021 Nov;142(5):807-825. (PMID: 34453582)
Biochim Biophys Acta Mol Cell Res. 2020 Nov;1867(11):118800. (PMID: 32712071)
Front Cell Dev Biol. 2021 Aug 03;9:668491. (PMID: 34414179)
Ageing Res Rev. 2022 Jan;73:101529. (PMID: 34813976)
Brain Sci. 2018 Feb 05;8(2):. (PMID: 29401741)
Gene. 2007 Nov 15;403(1-2):70-9. (PMID: 17855024)
Neurosci Lett. 2017 Apr 24;647:133-140. (PMID: 28330719)
Hum Mol Genet. 2017 Jul 15;26(14):2690-2700. (PMID: 28444230)
Am J Physiol Cell Physiol. 2007 Feb;292(2):C641-57. (PMID: 17092996)
Biochem Soc Trans. 2015 Oct;43(5):920-3. (PMID: 26517904)
Commun Biol. 2021 Jun 14;4(1):730. (PMID: 34127780)
Trends Cell Biol. 2018 Jan;28(1):67-76. (PMID: 28911913)
Int J Mol Sci. 2021 Apr 27;22(9):. (PMID: 33925691)
Biostatistics. 2012 Apr;13(2):204-16. (PMID: 22285995)
Cell Death Dis. 2022 Dec 20;13(12):1058. (PMID: 36539405)
Oxid Med Cell Longev. 2016;2016:3869610. (PMID: 27034734)
Alzheimers Dement. 2023 Apr;19(4):1598-1695. (PMID: 36918389)
Curr Neurol Neurosci Rep. 2013 Oct;13(10):381. (PMID: 23954969)
Neuron. 2016 Apr 6;90(1):11-25. (PMID: 27054615)
Nat Rev Mol Cell Biol. 2021 Feb;22(2):119-141. (PMID: 33353981)
Nat Rev Neurosci. 2018 Jan 19;19(2):63-80. (PMID: 29348666)
معلومات مُعتمدة: RF1AG057181 U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging); RF1 AG068034 United States AG NIA NIH HHS; RF1 AG081203 United States AG NIA NIH HHS; P30 AG013319 United States AG NIA NIH HHS; RF1AG068034 U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging); U19AG069701 U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging); RF1AG081203 U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging); P30 AG044271 United States AG NIA NIH HHS; R01 AG083981 United States AG NIA NIH HHS; U19 AG069701 United States AG NIA NIH HHS; RF1 AG057181 United States AG NIA NIH HHS; RF1 AG071226 United States AG NIA NIH HHS; RF1AG071226 U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)
المشرفين على المادة: 0 (ATP-Binding Cassette Transporters)
0 (ABCA7 protein, human)
0 (Abca7 protein, mouse)
تواريخ الأحداث: Date Created: 20231222 Date Completed: 20240605 Latest Revision: 20240613
رمز التحديث: 20240613
مُعرف محوري في PubMed: PMC11153016
DOI: 10.1038/s41380-023-02372-w
PMID: 38135757
قاعدة البيانات: MEDLINE
الوصف
تدمد:1476-5578
DOI:10.1038/s41380-023-02372-w