Complementation of mitochondrial electron transport chain by manipulation of the NAD + /NADH ratio
Open accessAbstract
Taking control of cellular NAD + concentrations: Cellular concentrations of the nicotinamide adenine dinucleotide (NAD + ) are critical for proper metabolism and are often altered in aging and disease. To enable better understanding of these processes, Titov et al. altered the concentration of NAD + in particular cellular compartments. They did this through expression of a bacterial enzyme targeted to specific compartments of human cells in culture. Their experiments emphasize the important role of the electron transport chain in redox transfer of electrons to NADH, rather than proton pumping, in mitochondrial pathogenesis. Science , this issue p. 231
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Respiration serves an anabolic role for proliferating cells by regenerating NAD+ from NADH.
“Instead, respiration serves an alternative anabolic role for proliferating cells by regenerating the oxidized form of nicotinamide adenine dinucleotide (NAD+) from the reduced form (NADH) (Birsoy et al., 2015; Sullivan et al., 2015; Titov et al., 2016).”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Titov et al., 2016
Mitochondrial ATP production appears dispensable for many proliferating cells.
“However, mitochondrial ATP production appears dispensable for many proliferating cells (Birsoy et al., 2015; Sullivan et al., 2015; Titov et al., 2016).”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Titov et al., 2016
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- Authors
- Titov, D. V., Cracan, V., Goodman, R. P., Peng, J., Grabarek, Z., & Mootha, V. K.
- Affiliations
- Broad Institute (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Titov, Denis V.
- Cracan, Valentin
- Mootha, Vamsi K.
- Venue
- Science
- Published
- 2016-04-08
- Volume
- 352
- Issue
- 6282
- Pages
- 231-235
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC4850741
- OpenAlex
- W2314595191
- Cited by
- 518
- References
- 51
- Citations by year
- 2026: 85 · 2025: 81 · 2024: 71 · 2023: 52 · 2022: 56 · 2021: 49 · 2020: 38 · 2019: 25 · 2018: 33 · 2017: 22 · 2016: 6
- FWCI
- 16.51
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- NIH (T-R01 R01GM099683, T32DK007191)
- Howard Hughes Medical Institute
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- mitochondrial electron transport chain, NAD+/NADH ratio, NADH oxidase, Lactobacillus brevis, reductive stress, mitochondrial redox state, gluconeogenesis, metabolic flux, mitochondrial dysfunction, ATP production
- MeSH terms
- Catalysis, Cytosol, Electron Transport, Genetic Complementation Test, Gluconeogenesis, HeLa Cells, Humans, Mitochondria, Multienzyme Complexes, NAD, NADH, NADPH Oxidoreductases, Oxidation-Reduction, Mitochondrial Diseases, Electron Transport Chain Complex Proteins, Levilactobacillus brevis
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