Induction of autophagy by depolarization of mitochondria
Autor(en): | Lyamzaev, Konstantin G. Tokarchuk, Artem V. Panteleeva, Alisa A. Mulkidjanian, Armen Y. Skulachev, Vladimir P. Chernyak, Boris V. |
Stichwörter: | ANTIOXIDANT; Autophagy; Cell Biology; CELLS; ENERGY; JC-1; MECHANISM; membrane potential; mild uncoupling; mitochondria; mitochondria-targeted cations; mitophagy; OXIDATIVE-PHOSPHORYLATION; PROTONOPHORE; UNCOUPLERS; YEAST | Erscheinungsdatum: | 2018 | Herausgeber: | TAYLOR & FRANCIS INC | Journal: | AUTOPHAGY | Volumen: | 14 | Ausgabe: | 5 | Startseite: | 921 | Seitenende: | 924 | Zusammenfassung: | 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 phosphorylationby various mitochondria-targeted penetrating cations may contribute to their reported therapeutic effects via inducing both autophagy and mitochondria-selective mitophagy. |
ISSN: | 15548627 | DOI: | 10.1080/15548627.2018.1436937 |
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