Induction of autophagy by depolarization of mitochondria
| Autor: | Armen Y. Mulkidjanian, Konstantin G. Lyamzaev, Artem V. Tokarchuk, Vladimir P. Skulachev, Boris V. Chernyak, Alisa A. Panteleeva |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Ubiquinone Mitochondrion Biology 03 medical and health sciences Organophosphorus Compounds Mitophagy Autophagy Humans Molecular Biology Letter to the Editor Cell Proliferation Membrane potential Membrane Potential Mitochondrial TOR Serine-Threonine Kinases Adenylate Kinase Depolarization Cell Biology Hep G2 Cells Basic Research Paper Cell biology Mitochondria 030104 developmental biology Mitochondrial Membranes Energy Metabolism Signal Transduction |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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