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Increased demand fo...
Increased demand for NAD + relative to ATP drives aerobic glycolysis
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- Luengo, Alba (author)
- Massachusetts Institute of Technology (MIT)
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- Li, Zhaoqi (author)
- Massachusetts Institute of Technology (MIT)
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- Gui, Dan Y. (author)
- Massachusetts Institute of Technology (MIT)
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- Sullivan, Lucas B. (author)
- Massachusetts Institute of Technology (MIT)
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- Zagorulya, Maria (author)
- Massachusetts Institute of Technology (MIT)
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- Do, Brian T. (author)
- Massachusetts Institute of Technology (MIT),Harvard Medical School
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- Ferreira, Raphael, 1990 (author)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Naamati, Adi (author)
- University Of Cambridge
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- Ali, Ahmed (author)
- Massachusetts Institute of Technology (MIT)
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- Lewis, Caroline A. (author)
- Whitehead Institute for Biomedical Research
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Thomas, Craig J. (author)
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- Spranger, Stefani (author)
- Massachusetts Institute of Technology (MIT)
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- Matheson, Nicholas J. (author)
- University Of Cambridge,Massachusetts Institute of Technology (MIT)
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- Vander Heiden, Matthew G. (author)
- Massachusetts Institute of Technology (MIT),Dana-Farber Cancer Institute
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(creator_code:org_t)
- Elsevier BV, 2021
- 2021
- English.
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In: Molecular Cell. - : Elsevier BV. - 1097-4164 .- 1097-2765. ; 81:4, s. 691-707.e6
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Abstract
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- Aerobic glycolysis, or preferential fermentation of glucose-derived pyruvate to lactate despite available oxygen, is associated with proliferation across many organisms and conditions. To better understand that association, we examined the metabolic consequence of activating the pyruvate dehydrogenase complex (PDH) to increase pyruvate oxidation at the expense of fermentation. We find that increasing PDH activity impairs cell proliferation by reducing the NAD+/NADH ratio. This change in NAD+/NADH is caused by increased mitochondrial membrane potential that impairs mitochondrial electron transport and NAD+ regeneration. Uncoupling respiration from ATP synthesis or increasing ATP hydrolysis restores NAD+/NADH homeostasis and proliferation even when glucose oxidation is increased. These data suggest that when demand for NAD+ to support oxidation reactions exceeds the rate of ATP turnover in cells, NAD+ regeneration by mitochondrial respiration becomes constrained, promoting fermentation, despite available oxygen. This argues that cells engage in aerobic glycolysis when the demand for NAD+ is in excess of the demand for ATP. Aerobic glycolysis is associated with proliferation in many biological contexts, yet what drives this phenotype has not been fully explained. Luengo et al. show that cells engage in aerobic glycolysis when the demand for NAD+ exceeds the demand for ATP, which leads to impaired NAD+ regeneration by mitochondrial respiration.
Subject headings
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
Keyword
- Warburg Effect
- Fermentation
- NAD
- PDK
- Cell Metabolism
- Aerobic Glycolysis
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Luengo, Alba
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Li, Zhaoqi
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Gui, Dan Y.
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Sullivan, Lucas ...
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Zagorulya, Maria
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Do, Brian T.
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show more...
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Ferreira, Raphae ...
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Naamati, Adi
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Ali, Ahmed
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Lewis, Caroline ...
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Thomas, Craig J.
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Spranger, Stefan ...
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Matheson, Nichol ...
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Vander Heiden, M ...
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- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Cell Biology
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Medical Biotechn ...
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and Medical Biotechn ...
- Articles in the publication
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Molecular Cell
- By the university
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Chalmers University of Technology