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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