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Retinal metabolism displays evidence for uncoupling of glycolysis and oxidative phosphorylation via Cori-, Cahill-, and mini-Krebs-cycle.

التفاصيل البيبلوغرافية
العنوان: Retinal metabolism displays evidence for uncoupling of glycolysis and oxidative phosphorylation via Cori-, Cahill-, and mini-Krebs-cycle.
المؤلفون: Chen Y; Institute for Ophthalmic Research, University of Tübingen, Tuebingen, Germany., Zizmare L; Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, University of Tübingen, Tuebingen, Germany.; Core Facility Metabolomics, Faculty of Medicine, University of Tübingen, Tuebingen, Germany., Calbiague V; Centro Interdisciplinario de Neurociencia de Valparaíso, Universidad de Valparaíso, Valparaíso, Chile., Wang L; Institute for Ophthalmic Research, University of Tübingen, Tuebingen, Germany., Yu S; Institute for Ophthalmic Research, University of Tübingen, Tuebingen, Germany., Herberg FW; Biochemistry Department, University of Kassel, Tuebingen, Germany., Schmachtenberg O; Centro Interdisciplinario de Neurociencia de Valparaíso, Universidad de Valparaíso, Valparaíso, Chile., Paquet-Durand F; Institute for Ophthalmic Research, University of Tübingen, Tuebingen, Germany., Trautwein C; Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, University of Tübingen, Tuebingen, Germany.; Core Facility Metabolomics, Faculty of Medicine, University of Tübingen, Tuebingen, Germany.
المصدر: ELife [Elife] 2024 May 13; Vol. 12. Date of Electronic Publication: 2024 May 13.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: eLife Sciences Publications, Ltd Country of Publication: England NLM ID: 101579614 Publication Model: Electronic Cited Medium: Internet ISSN: 2050-084X (Electronic) Linking ISSN: 2050084X NLM ISO Abbreviation: Elife Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Cambridge, UK : eLife Sciences Publications, Ltd., 2012-
مواضيع طبية MeSH: Glycolysis* , Oxidative Phosphorylation* , Citric Acid Cycle* , Retina*/metabolism, Animals ; Mice ; Energy Metabolism ; Metabolomics ; Retinal Pigment Epithelium/metabolism ; Retinal Rod Photoreceptor Cells/metabolism ; Mice, Inbred C57BL ; Retinal Cone Photoreceptor Cells/metabolism
مستخلص: The retina consumes massive amounts of energy, yet its metabolism and substrate exploitation remain poorly understood. Here, we used a murine explant model to manipulate retinal energy metabolism under entirely controlled conditions and utilised 1 H-NMR spectroscopy-based metabolomics, in situ enzyme detection, and cell viability readouts to uncover the pathways of retinal energy production. Our experimental manipulations resulted in varying degrees of photoreceptor degeneration, while the inner retina and retinal pigment epithelium were essentially unaffected. This selective vulnerability of photoreceptors suggested very specific adaptations in their energy metabolism. Rod photoreceptors were found to rely strongly on oxidative phosphorylation, but only mildly on glycolysis. Conversely, cone photoreceptors were dependent on glycolysis but insensitive to electron transport chain decoupling. Importantly, photoreceptors appeared to uncouple glycolytic and Krebs-cycle metabolism via three different pathways: (1) the mini-Krebs-cycle, fuelled by glutamine and branched chain amino acids, generating N -acetylaspartate; (2) the alanine-generating Cahill-cycle; (3) the lactate-releasing Cori-cycle. Moreover, the metabolomics data indicated a shuttling of taurine and hypotaurine between the retinal pigment epithelium and photoreceptors, likely resulting in an additional net transfer of reducing power to photoreceptors. These findings expand our understanding of retinal physiology and pathology and shed new light on neuronal energy homeostasis and the pathogenesis of neurodegenerative diseases.
Competing Interests: YC, LZ, VC, LW, SY, FH, OS, FP, CT No competing interests declared
(© 2023, Chen, Zizmare et al.)
References: PLoS One. 2014 Jul 16;9(7):e102392. (PMID: 25029531)
J Neurosci Res. 2001 Dec 1;66(5):914-22. (PMID: 11746419)
Cell Metab. 2022 Sep 6;34(9):1248-1263.e6. (PMID: 35987203)
Biochemistry. 1998 Oct 6;37(40):13958-67. (PMID: 9760230)
Elife. 2017 Jun 09;6:. (PMID: 28598329)
Proc Natl Acad Sci U S A. 1976 Sep;73(9):3141-5. (PMID: 9641)
Pflugers Arch. 2020 Sep;472(9):1299-1343. (PMID: 32789766)
Trans Am Clin Climatol Assoc. 1968;79:13-20. (PMID: 5667163)
FASEB J. 2022 Aug;36(8):e22428. (PMID: 35766190)
FEBS J. 2023 Feb;290(4):878-891. (PMID: 34923749)
Elife. 2017 Sep 13;6:. (PMID: 28901286)
Neurochem Res. 1999 Nov;24(11):1339-46. (PMID: 10555773)
Sci Rep. 2018 Sep 28;8(1):14517. (PMID: 30266938)
Nat Protoc. 2021 Aug;16(8):3802-3835. (PMID: 34215862)
Nat Genet. 2001 Dec;29(4):447-52. (PMID: 11694879)
Nat Rev Mol Cell Biol. 2006 Jul;7(7):517-28. (PMID: 16829982)
Biochemistry. 1992 Oct 27;31(42):10414-20. (PMID: 1420159)
Sci Rep. 2021 Feb 26;11(1):4742. (PMID: 33637845)
Science. 2001 Apr 20;292(5516):504-7. (PMID: 11283355)
Eye Brain. 2010;2:99-116. (PMID: 23226947)
Front Neuroenergetics. 2013 Dec 26;5:11. (PMID: 24421768)
J Cell Biol. 1967 Apr;33(1):61-72. (PMID: 6033942)
Mol Pharmacol. 1988 Apr;33(4):449-53. (PMID: 3357486)
Mol Vis. 2016 Jul 23;22:847-85. (PMID: 27499608)
J Neurosci. 1995 Oct;15(10):6377-88. (PMID: 7472402)
Invest Ophthalmol Vis Sci. 1997 Jan;38(1):48-55. (PMID: 9008629)
J Biol Chem. 2016 Feb 26;291(9):4698-710. (PMID: 26677218)
Dev Neurosci. 1993;15(3-5):181-93. (PMID: 7805570)
J Gen Physiol. 1981 Jun;77(6):667-92. (PMID: 6267165)
Metabolism. 1973 Feb;22(2):179-207. (PMID: 4567003)
Nat Genet. 1998 Dec;20(4):344-51. (PMID: 9843205)
Int J Mol Sci. 2023 Oct 17;24(20):. (PMID: 37894958)
Oncogene. 2011 Oct 20;30(42):4297-306. (PMID: 21516121)
Nature. 1977 Aug 18;268(5621):654-5. (PMID: 19708)
J Clin Invest. 2015 Apr;125(4):1446-58. (PMID: 25798619)
J Cereb Blood Flow Metab. 2013 Aug;33(8):1235-41. (PMID: 23673435)
Mol Cell. 2015 Jun 18;58(6):947-58. (PMID: 26091343)
Cell. 2015 May 7;161(4):817-32. (PMID: 25957687)
Prog Neurobiol. 2007 Feb;81(2):89-131. (PMID: 17275978)
Nucleic Acids Res. 2021 Jul 2;49(W1):W388-W396. (PMID: 34019663)
Biochim Biophys Acta. 1962 Sep 10;63:210-2. (PMID: 13979247)
Front Cell Dev Biol. 2020 Apr 30;8:266. (PMID: 32426353)
Hepatology. 2008 Apr;47(4):1363-70. (PMID: 18366115)
Bioengineering (Basel). 2023 Jun 15;10(6):. (PMID: 37370656)
Elife. 2024 May 13;12:. (PMID: 38739438)
Biochim Biophys Acta. 2011 Jun;1807(6):568-76. (PMID: 20804724)
Can J Physiol Pharmacol. 1992;70 Suppl:S158-64. (PMID: 1295666)
Hepatology. 2005 Feb;41(2):380-2. (PMID: 15660433)
Invest Ophthalmol Vis Sci. 1992 Feb;33(2):377-83. (PMID: 1740368)
Proc Natl Acad Sci U S A. 2020 Aug 11;117(32):19599-19603. (PMID: 32719136)
Neurobiol Dis. 2023 Aug;184:106211. (PMID: 37352985)
Am J Physiol Endocrinol Metab. 2008 Aug;295(2):E242-53. (PMID: 18577699)
Brain Res. 1991 Jan 25;539(2):337-41. (PMID: 2054602)
Exp Eye Res. 1990 Feb;50(2):213-8. (PMID: 2311683)
Annu Rev Biochem. 1946;15:193-218. (PMID: 20995968)
Brain Res. 2017 Oct 1;1672:50-57. (PMID: 28760441)
Proc Natl Acad Sci U S A. 2020 Nov 17;117(46):28816-28827. (PMID: 33144507)
Z Anat Entwicklungsgesch. 1973 Oct 31;142(2):219-38. (PMID: 4781863)
Biochem J. 1929;23(3):536-45. (PMID: 16744238)
Curr Biol. 2008 Dec 23;18(24):1917-21. (PMID: 19084410)
J Neurosci. 2007 Sep 19;27(38):10311-9. (PMID: 17881537)
Magn Reson Med Sci. 2015;14(1):13-24. (PMID: 25500779)
J Biol Chem. 1994 Nov 4;269(44):27414-20. (PMID: 7961653)
Epilepsia. 2003 Sep;44(9):1153-9. (PMID: 12919386)
J Vis Exp. 2020 Nov 25;(165):. (PMID: 33311434)
Mol Vis. 2012;18:2673-86. (PMID: 23170060)
J Neurosci. 1998 Nov 1;18(21):8936-46. (PMID: 9786999)
Oncol Lett. 2012 Dec;4(6):1151-1157. (PMID: 23226794)
Toxicol Lett. 2011 Jun 24;203(3):200-9. (PMID: 21402135)
Physiol Rev. 2005 Jul;85(3):845-81. (PMID: 15987797)
Invest Ophthalmol Vis Sci. 1994 Oct;35(11):3910-21. (PMID: 7928189)
J Comp Neurol. 2010 Sep 1;518(17):3604-17. (PMID: 20593360)
Invest Ophthalmol Vis Sci. 2005 Dec;46(12):4728-33. (PMID: 16303972)
Am J Physiol Cell Physiol. 2019 Jan 1;316(1):C121-C133. (PMID: 30462537)
J Neurochem. 2022 Jan;160(2):283-296. (PMID: 34726780)
Invest Ophthalmol Vis Sci. 2021 May 3;62(6):11. (PMID: 33974046)
Drug Metab Dispos. 2020 May;48(5):378-385. (PMID: 32156684)
معلومات مُعتمدة: 1210790 Fondo Nacional de Desarrollo Científico y Tecnológico; 21180443 Becas Chile/2018
فهرسة مساهمة: Keywords: aerobic glycolysis; glucose transport; glucose-alanine cycle; mouse; neuroscience; photoreceptor metabolism; retinal metabolism; retinitis pigmentosa
سلسلة جزيئية: Dryad 10.5061/dryad.c2fqz61hr
تواريخ الأحداث: Date Created: 20240513 Date Completed: 20240513 Latest Revision: 20240515
رمز التحديث: 20240515
مُعرف محوري في PubMed: PMC11090511
DOI: 10.7554/eLife.91141
PMID: 38739438
قاعدة البيانات: MEDLINE
الوصف
تدمد:2050-084X
DOI:10.7554/eLife.91141