Mitoquinone shifts energy metabolism to reduce ROS-induced oxeiptosis in female granulosa cells and mouse oocytes

Abstract

The female reproductive system is quite sensitive to regulation, and external environmental stimuli may cause oxidative stress which in turn may lead to accelerated aging and programmed cell death in female reproductive cells. The aim of this study was to investigate whether or not mitoquinone (MitoQ) could resist ROS-induced apoptosis in human granulosa cells and mouse oocytes. We found that the MitoQ treatment significantly reduced production of reactive oxygen species (ROS) and imbalance in mitochondrial membrane potential. The MitoQ treatment prevented an excessive mitochondrial fragmentation by upregulating Drp1 S637 and decreasing Drp1 S637 phosphorylation. More importantly, MitoQ maintained aerobic respiration and reduced anaerobic respiration by regulating reprogramming of intracellular energy metabolism, which enhanced cellular ATP production. MitoQ effectively reduced the expressions of AIFM1 and PGAM5, key molecules whose expressions were reversed not only in granulosa cells but also in mouse oocytes. Our findings suggest that MitoQ can ameliorate the mitochondrial deterioration caused by ROS and reprogram cellular energy metabolism, providing protection to cells against apoptosis. The presence of MitoQ may help in protecting human germ cells under in vitro culture conditions.

Phenethyl isothiocyanate and dasatinib combination synergistically reduces hepatocellular carcinoma growth via cell cycle arrest and oxeiptosis

“…However, high levels of oxidative stress induce PGAM5 release and translocation into the mitochondria, where it dephosphorylates AIFM1, the main effector of oxeiptosis. PDc was shown to decrease Keap1 accumulation, which is in contrast with what was described by Kang et al ( Kang et al, 2022 ), but in line with what was reported in Holze et al and Li et al works, in which higher levels of ROS oxidise Keap1 ( Holze et al, 2018 ; Tsui and Li, 2023 ). Moreover, recent work showed that Keap1 expression increases only in the first 2 h of ROS induction and then drops drastically ( Pallichankandy et al, 2023 ).…”

“…It has been shown that PGAM5 cleavage increases in conditions of stress, triggering different types of cell death ( Cheng et al, 2021 ). To corroborate this thesis, Li et al observed an increased cleavage of PGAM5 in conditions of high levels of ROS that induced oxeiptosis ( Tsui and Li, 2023 ). Interestingly, PGAM5 cleavage happens when it is located into the internal mitochondrial membrane ( Sekine et al, 2012 ), which is where AIFM1 is located.…”

CX43 and oxidative stress are the targets of BCB staining to predict the developmental potential of buffalo oocytes

“…Reactive oxygen species (ROS) is a critical factor for the maturation of germ cells. ROS is an active oxygen molecule that can be produced and removed in a living body through synthesis, decomposition, and operation (19). However, excessive reactive oxygen can damage germ cells and affect their maturation.…”

Eukaryotic Elongation Factor 2 Kinase EFK-1/eEF2K promotes starvation resistance by preventing oxidative damage inC. elegans

“…The mitochondria are an important site of ROS production (66), and decline of mitochondrial quality during starvation (61,63,67) correlates with oxidative stress phenotypes of starved worms. To determine if the mitochondria are a source of the increased ROS levels observed in starved efk-1 mutants, we examined whether the starvation defect of the efk-1 mutant was altered by the mitochondrially targeted antioxidant mitoquinone (MitoQ) (68,69), which ameliorates stress-induced mitochondrial ROS generation and protects against mitochondrial dysfunction-induced phenotypes in mammalian cells and C. elegans (69)(70)(71). Indeed, MitoQ supplementation partially rescued the starvation survival defect of efk-1 mutants (Figure 7H; Figure S7I).…”