Dataset Information

MitoQ regulates autophagy by inducing a pseudo-mitochondrial membrane potential.

ABSTRACT: During the process of oxidative phosphorylation, protons are pumped into the mitochondrial intermembrane space to establish a mitochondrial membrane potential (MMP). The electrochemical gradient generated allows protons to return to the matrix through the ATP synthase complex and generates ATP in the process. MitoQ is a lipophilic cationic drug that is adsorbed to the inner mitochondrial membrane; however, the cationic moiety of MitoQ remains in the intermembrane space. We found that the positive charges in MitoQ inhibited the activity of respiratory chain complexes I, III, and IV, reduced proton production, and decreased oxygen consumption. Therefore, a pseudo-MMP (PMMP) was formed via maintenance of exogenous positive charges. Proton backflow was severely impaired, leading to a decrease in ATP production and an increase in AMP production. Excess AMP activates AMP kinase, which inhibits the MTOR (mechanistic target of rapamycin) pathway and induces macroautophagy/autophagy. Therefore, we conclude that MitoQ increases PMMP via proton displacement with exogenous positive charges. In addition, PMMP triggered autophagy in hepatocellular carcinoma HepG2 cells via modification of mitochondrial bioenergetics pathways.

SUBMITTER: Sun C

PROVIDER: S-EPMC5388232 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

MitoQ regulates autophagy by inducing a pseudo-mitochondrial membrane potential.

Sun Chao C Liu Xiongxiong X Di Cuixia C Wang Zhenhua Z Mi Xiangquan X Liu Yang Y Zhao Qiuyue Q Mao Aihong A Chen Weiqiang W Gan Lu L Zhang Hong H

Autophagy 20170125 4

During the process of oxidative phosphorylation, protons are pumped into the mitochondrial intermembrane space to establish a mitochondrial membrane potential (MMP). The electrochemical gradient generated allows protons to return to the matrix through the ATP synthase complex and generates ATP in the process. MitoQ is a lipophilic cationic drug that is adsorbed to the inner mitochondrial membrane; however, the cationic moiety of MitoQ remains in the intermembrane space. We found that the positiv ...[more]

PMID: 28121478

Similar Datasets

Project description:Starting from the discovery of phototherapy in the beginning of the last century, photobiomodulation (PBM) has been defined in late 1960s and, since then, widely described in different in vitro models. Robust evidence indicates that the effect of light exposure on the oxidative state of the cells and on mitochondrial dynamics, suggesting a great therapeutic potential. The translational scale-up of PBM, however, has often given contrasting and confusing results, mainly due to light exposure protocols which fail to adequately control or define factors such as emitting device features, emitted light characteristics, exposure time, cell target, and readouts. In this in vitro study, we describe the effects of a strictly controlled light-emitting diode (LED)-based PBM protocol on human fibroblasts, one of the main cells involved in skin care, regeneration, and repair. We used six emitter probes at different wavelengths (440, 525, 645, 660, 780, and 900 nm) with the same irradiance value of 0.1 mW/cm2, evenly distributed over the entire surface of the cell culture well. The PBM was analyzed by three main readouts: (i) mitochondrial potential (MitoTracker Orange staining), (ii) reactive oxygen species (ROS) production (CellROX staining); and (iii) cell death (nuclear morphology). The assay was also implemented by cell-based high-content screening technology, further increasing the reliability of the data. Different exposure protocols were also tested (one, two, or three subsequent 20 s pulsed exposures at 24 hr intervals), and the 645 nm wavelength and single exposure chosen as the most efficient protocol based on the mitochondrial potential readout, further confirmed by mitochondrial fusion quantification. This protocol was then tested for its potential to prevent H2O2-induced oxidative stress, including modulation of the light wave frequency. Finally, we demonstrated that the controlled PBM induced by the LED light exposure generates a preconditioning stimulation of the mitochondrial potential, which protects the cell from oxidative stress damage.

Dataset Information

MitoQ regulates autophagy by inducing a pseudo-mitochondrial membrane potential.

Publications

MitoQ regulates autophagy by inducing a pseudo-mitochondrial membrane potential.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets