Mitochondrial dysfunction and excessive reactive oxygen species production contributes to the pathophysiology of aging. Coenzyme Q10 is thought to protect mitochondria from oxidative damage; thus, mitoquinone was developed as mitochondria-targeted analogue with similar antioxidant activity. Mitoquinone is the oxidized form of mitoquinol. Mitoquinone/mitoquinol mesylate has been proposed as a food ingredient. As part of the safety analysis, we performed genotoxicity assays and a 39-week toxicity study to determine overall toxicity potential. Mitoquinone mesylate showed no evidence of genotoxic potential in two in vitro assays, bacterial reverse mutation and human lymphocyte chromosome aberration, nor in the in vivo micronucleus test in rats. In the 39-week study in dogs, there were no findings observed, which were considered to represent adverse systemic toxicity; therefore, the high dose level (40 mg/kg/day) was considered the NOAEL. The principal findings in this study were fecal disturbances and vomiting. These findings were considered to be due to a local, possibly irritant effect of the test substance on the gastrointestinal tract and were not considered adverse as there were no impacts on clinical or histopathology. This highest dose exceeds the expected daily human intake more than 100-fold. Data from well-designed clinical trials actively collecting safety endpoints corroborate that 20 mg/day can be safely consumed and is not likely to result in significant gastrointestinal complaints. These results support the conclusion that the use of mitoquinone/mitoquinol mesylate as a food ingredient is safe.

Despite the clinical advances in cancer treatment, the high mortality rate is still a great challenge, requiring much effort to find new and efficient cancer therapies.
OBJECTIVE: The present evidence investigated the potential antiproliferative impact of the mitochondrial-targeted antioxidant, Mitoquinol (MitoQ), on a mouse model of Ehrlich ascites carcinoma (EAC).
METHODS: Mice-bearing tumors were administered two doses of MitoQ (0.3 mg & 0.5 mg/kg; i.p daily) or doxorubicin (2 mg/kg; i.p daily) for 20 days.
RESULTS: EAC mice revealed exacerbated mitochondrial reactive oxygen species (mtROS) and impaired mitochondrial membrane potential (△Ψm). Dysfunctional mitophagy was observed in EAC mice, along with boosting aerobic glycolysis. In addition, tumor cells exhibited higher proliferation rates, thereby stimulating cell cycle, invasion, and angiogenesis biomarkers together with suppressing proapoptotic proteins, events that might be correlated with activation of NF-κB signaling. The administration of MitoQ combated tumor cell survival and dissemination in EAC mice as evidenced by reducing tumor volumes and weights and increasing the number of necrotic areas in histopathological assessment. MitoQ also repressed tumor cell cycle, invasion, and angiogenesis via preventing cyclin D1 mRNA, MMP-1, and CD34 levels as well as VEGF protein expression. These observations were associated with the abrogation of mtROS overproduction and enhancement of the mitophagy proteins, PINK1/Parkin levels, followed by inhibition of NADH dehydrogenase. Notably, NF-κB signaling was modulated.
CONCLUSIONS: This study suggests that MitoQ combated tumor cell survival and progression in EAC mice by maintaining mtROS and restoring mitophagy, thereby attenuation of NF-κB activation.

Aging is associated with reduced fitness and increased myeloid bias of the hematopoietic stem cell (HSC) compartment, causing increased risk of immune compromise, anemia, and malignancy. We show that mitochondrial membrane potential (MMP) can be used to prospectively isolate chronologically old HSCs with transcriptional features and functional attributes characteristic of young HSCs, including a high rate of transcription and balanced lineage-affiliated programs. Strikingly, MMP is a stronger determinant of the quantitative and qualitative transcriptional state of HSCs than chronological age, and transcriptional consequences of manipulation of MMP in HSCs within their native niche suggest a causal relationship. Accordingly, we show that pharmacological enhancement of MMP in old HSCs in vivo increases engraftment potential upon transplantation and reverses myeloid-biased peripheral blood output at steady state. Our results demonstrate that MMP is a source of heterogeneity in old HSCs, and its pharmacological manipulation can alter transcriptional programs with beneficial consequences for function.