Fluoxetine interacts with the lipid bilayer of the inner membrane in isolated rat brain mitochondria, inhibiting electron transport and F1F0-ATPase activity
Abstract
The effects of fluoxetine on the oxidative phosphorylation of mitochondria isolated from rat brain and on the kinetic properties of submitochondrial particle F1F0-ATPase were evaluated. The state 3 respiration rate supported by pyruvate + malate, succinate, or ascorbate + tetramethyl-p-phenylenediamine (TMPD) was substantially decreased by fluoxetine. The IC50 for pyruvate + malate oxidation was approximately 0.15 mM and the pattern of inhibition was the typical one of the electron-transport inhibitors, in that the drug inhibited both ADP- and carbonyl cyanide m-chlorophenylhydrazone (CCCP)-stimulated respirations and the former inhibition was not released by the uncoupler. Fluoxetine also decreased the activity of submitochondrial particle F1F0-ATPase (IC50 approximately 0.08 mM) even though K0.5 and activity of Triton X-100 solubilized enzyme were not changed substantially. As a consequence of these effects, fluoxetine decreased the rate of ATP synthesis and depressed the phosphorylation potential of mitochondria. Incubation of mitochondria or submitochondrial particles with fluoxetine under the conditions of respiration or F1F0-ATPase assays, respectively, caused a dose-dependent enhancement of 1-anilino-8-naphthalene sulfonate (ANS) fluorescence. These results show that fluoxetine indirectly and nonspecifically affects electron transport and F1F0)-ATPase activity inhibiting oxidative phosphorylation in isolated rat brain mitochondria. They suggest, in addition, that these effects are mediated by the drug interference with the physical state of lipid bilayer of inner mitochondrial membrane.
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Fluoxetine can indirectly and nonspecifically affect electron transport and F1F0-ATPase activity, thereby inhibiting oxidative phosphorylation in rat brain.
“Curti et al. (1999) reported that fluoxetine can indirectly and nonspecifically affect electron transport and F1F0-ATPase activity, thereby inhibiting oxidative phosphorylation in rat brain [6].”
From Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder (2012) · cites this paper as [6]
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Hilgendorf, J., Calisto, V., Campos, D., Cardoso, D. N., Fernandes, J., Lima, D. L. D., Sørensen, J. G., Sousa, É. M. L., & Loureiro, S. (2026) · Environmental Science & Technology · doi:10.1021/acs.est.5c12822
- Authors
- Curti, C., Mingattao, F. E., Polizello, A. C. M., Galastri, L. O., Uyemura, S. A., & Santos, A. C.
- Affiliations
- Universidade de São Paulo (BR)
- Venue
- Molecular and Cellular Biochemistry
- Published
- 1999-09
- Volume
- 199
- Issue
- 1-2
- Pages
- 103-109
- ISSN
- 0300-8177 (ISSN-L)
- 1573-4919
- OpenAlex
- W1488797294
- Semantic Scholar
- 91567299985794ed590a98ca8c65c89ba439fe2c
- Cited by
- 74
- References
- 27
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 3 · 2023: 6 · 2022: 1 · 2021: 6 · 2020: 3 · 2019: 4 · 2018: 4 · 2017: 4 · 2016: 5 · 2015: 5 · 2014: 1 · 2013: 3 · 2012: 8
- FWCI
- 0.23
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Molecular and Cellular Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › ATP Synthase and ATPases Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- fluoxetine, brain mitochondria, inner mitochondrial membrane, lipid bilayers, electron transport inhibition, F1F0-ATPase, oxidative phosphorylation, ATP production, state 3 respiration
- MeSH terms
- Adenosine Triphosphate, Anilino Naphthalenesulfonates, Animals, Brain, Fluorescent Dyes, Fluoxetine, Proton-Translocating ATPases, Intracellular Membranes, Kinetics, Lipid Bilayers, Male, Mitochondria, Oxygen Consumption, Phosphorylation, Rats, Wistar, Antidepressive Agents, Second-Generation, Cell Respiration, Rats, In Vitro Techniques
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