Induction of autophagy by depolarization of mitochondria
Open accessAbstract
Mitochondrial dysfunction plays a crucial role in the macroautophagy/autophagy cascade. In a recently published study Sun et al. described the induction of autophagy by the membranophilic triphenylphosphonium (TPP)-based cation 10-(6'-ubiquinonyl) decyltriphenylphosphonium (MitoQ) in HepG2 cells (Sun C, et al. "MitoQ regulates autophagy by inducing a pseudo-mitochondrial membrane potential [PMMP]", Autophagy 2017, 13:730-738.). Sun et al. suggested that MitoQ adsorbed to the inner mitochondrial membrane with its cationic moiety remaining in the intermembrane space, adding a large number of positive charges and establishing a "pseudo-mitochondrial membrane potential," which blocked the ATP synthase. Here we argue that the suggested mechanism for generation of the "pseudo-mitochondrial membrane potential" is physically implausible and contradicts earlier findings on the electrophoretic displacements of membranophilic cations within and through phospholipid membranes. We provide evidence that TPP-cations dissipated the mitochondrial membrane potential in HepG2 cells and that the induction of autophagy in carcinoma cells by TPP-cations correlated with the uncoupling of oxidative phosphorylation. The mild uncoupling of oxidative phosphorylation by various mitochondria-targeted penetrating cations may contribute to their reported therapeutic effects via inducing both autophagy and mitochondria-selective mitophagy.
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Mitochondrial uncoupling is often associated with autophagy activation, and more specifically with mitophagy.
“Mitochondrial uncoupling has often been associated with autophagy activation, and more specifically, with mitophagy (specific degradation of mitochondria by macroautophagy) (Figure 1).”
From Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases (2019) · cites this paper as [90]
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- Authors
- Lyamzaev, K. G., Tokarchuk, A. V., Panteleeva, A. A., Mulkidjanian, A. Y., Skulachev, V. P., & Chernyak, B. V.
- Affiliations
- Lomonosov Moscow State University (RU)
- Osnabrück University (DE)
- Corresponding author
- Lyamzaev, Konstantin G.
- Chernyak, Boris V.
- ORCID
- Venue
- Autophagy
- Publisher
- Informa UK Limited
- Published
- 2018-03-13
- Volume
- 14
- Issue
- 5
- Pages
- 921-924
- ISSN
- 1554-8627 (ISSN-L)
- 1554-8635
- PMC
- PMC6070013
- OpenAlex
- W2791957311
- Cited by
- 121
- References
- 24
- Citations by year
- 2026: 8 · 2025: 17 · 2024: 21 · 2023: 16 · 2022: 14 · 2021: 18 · 2020: 19 · 2019: 7 · 2018: 1
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Autophagy (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Russian Scientific Foundation (17-14-01314)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › ATP Synthase and ATPases Research
- Keywords
- mitochondrial depolarization, MitoQ, triphenylphosphonium cation, mitochondrial membrane potential, mitochondrial uncoupling, ATP synthase inhibition, mitophagy, HepG2 cells, mitochondrial dysfunction
- MeSH terms
- Autophagy, Mitochondria, Mitochondrial Membranes, Membrane Potential, Mitochondrial, Mitophagy
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