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Aerobic Glycolysis in Photoreceptors Supports Energy Demand in the Absence of Mitochondrial Coupling

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Retinal Degenerative Diseases XIX

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1415))

Abstract

Metabolism is adapted to meet energetic needs. Based on the amount of ATP required to maintain plasma membrane potential, photoreceptor energy demands must be high. The available evidence suggests that photoreceptors primarily generate metabolic energy through aerobic glycolysis, though this evidence is based primarily on protein expression and not measurement of metabolic flux. Aerobic glycolysis can be validated by measuring flux of glucose to lactate. Aerobic glycolysis is also inefficient and thus an unexpected adaptation for photoreceptors to make. We measured metabolic rates to determine the energy-generating pathways that support photoreceptor metabolism. We found that photoreceptors indeed perform aerobic glycolysis and this is associated with mitochondrial uncoupling.

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Abbreviations

ATP:

Adenosine triphosphate

GC-MS:

Gas chromatography-mass spectrometry

GCR:

Glucose consumption rate

HK2:

Hexokinase 2

LPR:

Lactate production rate

NADH:

Nicotinamide adenine dinucleotide

NADPH:

Nicotinamide adenine dinucleotide phosphate

OCR:

Oxygen consumption rate

PKM2:

Pyruvate kinase M2

References

  1. Warburg O. The metabolism of carcinoma cells. J Cancer Res. 1925;9(1):148–63.

    Article  CAS  Google Scholar 

  2. Winkler BS. Glycolytic and oxidative metabolism in relation to retinal function. J Gen Physiol. 1981;77(6):667–92.

    Article  CAS  PubMed  Google Scholar 

  3. Okawa H, Sampath AP, Laughlin SB, Fain GL. ATP consumption by mammalian rod photoreceptors in darkness and in light. Curr Biol. 2008;18(24):1917–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Ames A, Li Y-Y, Heher EC, Kimble CR. Energy metabolism of rabbit retina as related to function: high cost of Na+ transport. J Neurosci. 1992;12(3):940–53.

    Article  Google Scholar 

  5. Lindsay KJ, Du J, Sloat SR, Contreras L, Linton JD, Turner SJ, et al. Pyruvate kinase and aspartate-glutamate carrier distributions reveal key metabolic links between neurons and glia in retina. Proc Natl Acad Sci U S A. 2014;111(43):15579.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Ferguson EC, Rathmell JC. New roles for pyruvate kinase M2: working out the Warburg effect. Trends Biochem Sci. 2008;33(8):359–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Wolf A, Agnihotri S, Micallef J, Mukherjee J, Sabha N, Cairns R, et al. Hexokinase 2 is a key mediator of aerobic glycolysis and promotes tumor growth in human glioblastoma multiforme. J Exp Med. 2011;208(2):313–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Petit L, Ma S, Cipi J, Cheng S-Y, Zieger M, Hay N, et al. Aerobic glycolysis is essential for normal rod function and controls secondary cone death in retinitis pigmentosa. Cell Rep. 2018;23(9):2629.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Chinchore Y, Begaj T, Wu D, Drokhlyansky E, Cepko C. Glycolytic reliance promotes anabolism in photoreceptors. elife. 2017;6:e25946.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Singh RK, Kolandaivelu S, Ramamurthy V. Early alteration of retinal neurons in Aipl1−/− animals. Invest Ophthalmol Vis Sci. 2014;55(5):3081–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Lowry OH, Passonneau JV. A flexible system of enzymatic analysis. Elsevier; 1972.

    Google Scholar 

  12. Millard P, Delépine B, Guionnet M, Heuillet M, Bellvert F, Létisse F. IsoCor: isotope correction for high-resolution MS labeling experiments. Bioinformatics. 2019;35(21):4484–7.

    Article  CAS  PubMed  Google Scholar 

  13. Neal A, Rountree A, Philips C, Kavanagh T, Williams DP, Newham P, et al. Quantification of low-level drug effects using real-time, in vitro measurement of oxygen consumption rate. Toxicol Sci. 2015;148(2):594–602.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Lewis CA, Parker SJ, Fiske BP, Mccloskey D, Gui DY, Green CR, et al. Article tracing compartmentalized NADPH metabolism in the cytosol and mitochondria of mammalian cells. Mol Cell. 2014;55:253–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Pasteur L. Expériences et vues nouvelles sur la nature des fermentations. Comptes rendus l’Académie des Sci. 1861;52:1260–4.

    Google Scholar 

  16. Brand M, Nicholls D. Assessing mitochondrial dysfunction in cells. Biochem J. 2011;435(2):297–312.

    Article  CAS  PubMed  Google Scholar 

  17. Du J, Rountree A, Cleghorn WM, Contreras L, Lindsay KJ, Sadilek M, et al. Phototransduction influences metabolic flux and nucleotide metabolism in mouse retina. J Biol Chem. 2016;291(9):4698–710.

    Article  CAS  PubMed  Google Scholar 

  18. Bisbach CM, Hass DT, Robbings BM, Rountree AM, Sadilek M, Sweet IR, et al. Succinate can shuttle reducing power from the hypoxic retina to the O2-rich pigment epithelium. Cell Rep. 2020;31(5):107606.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Roesch K, Stadler MB, Cepko CL. Gene expression changes within Müller glial cells in retinitis pigmentosa. Mol Vis. 2012;18:1197.

    PubMed  PubMed Central  Google Scholar 

  20. Scholz R, Sobotka M, Caramoy A, Stempfl T, Moehle C, Langmann T. Minocycline counter-regulates pro-inflammatory microglia responses in the retina and protects from degeneration. J Neuroinflammation. 2015;12(1):1–14.

    Google Scholar 

  21. Wang L, Pavlou S, Du X, Bhuckory M, Xu H, Chen M. Glucose transporter 1 critically controls microglial activation through facilitating glycolysis. Mol Neurodegener. 2019;14(1):1–15.

    Article  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Biochemistry, University of Washington, Seattle, WA, USA

    Daniel T. Hass, Celia M. Bisbach & James B. Hurley

  2. Department of Chemistry, University of Washington, Seattle, WA, USA

    Martin Sadilek

  3. UW Medicine - Diabetes Institute, University of Washington, Seattle, WA, USA

    Ian R. Sweet

Authors
  1. Daniel T. Hass
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  2. Celia M. Bisbach
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  3. Martin Sadilek
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  4. Ian R. Sweet
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  5. James B. Hurley
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Corresponding author

Correspondence to Daniel T. Hass .

Editor information

Editors and Affiliations

  1. Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    John D. Ash

  2. Ocular Genomics InstituteDepartment of OphthalmologyMassachusetts Eye and Ear InfirmaryHarvard Medical School, Boston, MA, USA

    Eric Pierce

  3. Health Sciences Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA

    Robert E. Anderson

  4. Department of Ophthalmology, Duke Medical Center, Durham, NC, USA

    Catherine Bowes Rickman

  5. Department of Ophthalmology, Cleveland Clinic Lerner College of Medicine, Cleveland, OH, USA

    Joe G. Hollyfield

  6. Laboratory for Retinal Cell BiologyDepartment of OphthalmologyUniversity Hospital Zurich, University of Zurich, Schlieren, Switzerland

    Christian Grimm

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© 2023 The Author(s), under exclusive license to Springer Nature Switzerland AG

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Hass, D.T., Bisbach, C.M., Sadilek, M., Sweet, I.R., Hurley, J.B. (2023). Aerobic Glycolysis in Photoreceptors Supports Energy Demand in the Absence of Mitochondrial Coupling. In: Ash, J.D., Pierce, E., Anderson, R.E., Bowes Rickman, C., Hollyfield, J.G., Grimm, C. (eds) Retinal Degenerative Diseases XIX. Advances in Experimental Medicine and Biology, vol 1415. Springer, Cham. https://doi.org/10.1007/978-3-031-27681-1_64

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