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Updated: Jul 5, 2025
Mitochondrial Respiration Quantification in Yeast Whole Cells
Published on: November 8, 2024
SkQ3 Exhibits the Most Pronounced Antioxidant Effect on Isolated Rat Liver Mitochondria and Yeast Cells
Anton G Rogov1, Tatyana N Goleva1, Dinara A Aliverdieva2
1National Research Center "Kurchatov Institute", 123182 Moscow, Russia.
Abstract:
Oxidative stress is involved in a wide range of age-related diseases. A critical role has been proposed for mitochondrial oxidative stress in initiating or promoting these pathologies and the potential for mitochondria-targeted antioxidants to fight them, making their search and testing a very urgent task. In this study, the mitochondria-targeted antioxidants SkQ1, SkQ3 and MitoQ were examined as they affected isolated rat liver mitochondria and yeast cells, comparing SkQ3 with clinically tested SkQ1 and MitoQ. At low concentrations, all three substances stimulated the oxidation of respiratory substrates in state 4 respiration (no ADP addition); at higher concentrations, they inhibited the ADP-triggered state 3 respiration and the uncoupled state, depolarized the inner mitochondrial membrane, contributed to the opening of the mPTP (mitochondrial permeability transition pore), did not specifically affect ATP synthase, and had a pronounced antioxidant effect. SkQ3 was the most active antioxidant, not possessing, unlike SkQ1 or MitoQ, prooxidant activity with increasing concentrations. In yeast cells, all three substances reduced prooxidant-induced intracellular oxidative stress and cell death and prevented and reversed mitochondrial fragmentation, with SkQ3 being the most efficient. These data allow us to consider SkQ3 as a promising potential therapeutic agent to mitigate pathologies associated with oxidative stress.
Insights
Mitochondria-targeted antioxidants like SkQ3 show promise for treating age-related diseases. SkQ3 effectively reduced oxidative stress and cell death in yeast cells, unlike other tested antioxidants.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Mitochondrial oxidative stress is implicated in numerous age-related diseases.
- Mitochondria-targeted antioxidants offer a potential therapeutic strategy.
- Urgent need exists for effective mitochondria-targeted antioxidants.
Purpose of the Study:
- To evaluate the efficacy of mitochondria-targeted antioxidants SkQ1, SkQ3, and MitoQ.
- To compare the antioxidant and pro-oxidant activities of SkQ3, SkQ1, and MitoQ.
- To assess their effects on isolated rat liver mitochondria and yeast cells.
Main Methods:
- Assessment of isolated rat liver mitochondria respiration (state 4 and state 3).
- Evaluation of inner mitochondrial membrane potential and mitochondrial permeability transition pore (mPTP) opening.
- Analysis of antioxidant effects in yeast cells under prooxidant conditions.
Main Results:
- All tested antioxidants stimulated state 4 respiration at low concentrations and inhibited state 3 respiration at higher concentrations.
- Higher concentrations led to inner mitochondrial membrane depolarization and mPTP opening, without affecting ATP synthase.
- SkQ3 demonstrated the strongest antioxidant activity and lacked prooxidant effects, unlike SkQ1 and MitoQ.
- In yeast cells, all antioxidants reduced oxidative stress and cell death, with SkQ3 being most effective in preventing and reversing mitochondrial fragmentation.
Conclusions:
- SkQ3 exhibits potent antioxidant properties and a favorable safety profile compared to SkQ1 and MitoQ.
- SkQ3 effectively mitigates oxidative stress and mitochondrial damage in cellular models.
- SkQ3 represents a promising therapeutic candidate for pathologies linked to oxidative stress.
