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Propagation of Mitochondria-Derived Reactive Oxygen Species within the Dipodascus magnusii Cells
Anton G Rogov1, Tatiana N Goleva1, Khoren K Epremyan1
1Bach Institute of Biochemistry, Federal Research Center "Fundamentals of Biotechnology" of the Russian Academy of Sciences 33, bld. 2 Leninsky Ave., Moscow 119071, Russia.
Abstract:
Mitochondria are considered to be the main source of reactive oxygen species (ROS) in the cell. It was shown that in cardiac myocytes exposed to excessive oxidative stress, ROS-induced ROS release is triggered. However, cardiac myocytes have a network of densely packed organelles that do not move, which is not typical for the majority of eukaryotic cells. The purpose of this study was to trace the spatiotemporal development (propagation) of prooxidant-induced oxidative stress and its interplay with mitochondrial dynamics. We used Dipodascus magnusii yeast cells as a model, as they have advantages over other models, including a uniquely large size, mitochondria that are easy to visualize and freely moving, an ability to vigorously grow on well-defined low-cost substrates, and high responsibility. It was shown that prooxidant-induced oxidative stress was initiated in mitochondria, far preceding the appearance of generalized oxidative stress in the whole cell. For yeasts, these findings were obtained for the first time. Preincubation of yeast cells with SkQ1, a mitochondria-addressed antioxidant, substantially diminished production of mitochondrial ROS, while only slightly alleviating the generalized oxidative stress. This was expected, but had not yet been shown. Importantly, mitochondrial fragmentation was found to be primarily induced by mitochondrial ROS preceding the generalized oxidative stress development.
Insights
Oxidative stress begins in mitochondria, leading to cellular damage. This study reveals mitochondrial ROS triggers fragmentation before widespread cell stress, using yeast as a model.
Area of Science:
- Cell Biology
- Mitochondrial Biology
- Oxidative Stress Research
Background:
- Mitochondria are primary sources of reactive oxygen species (ROS) in cells.
- ROS-induced ROS release occurs in cardiac myocytes under oxidative stress.
- Cardiac myocytes possess unique, immobile organelle networks, unlike most eukaryotic cells.
Purpose of the Study:
- To investigate the spatiotemporal propagation of prooxidant-induced oxidative stress.
- To examine the interplay between oxidative stress and mitochondrial dynamics.
- To utilize *Dipodascus magnusii* yeast as a model for these investigations.
Main Methods:
- Employing *Dipodascus magnusii* yeast cells, chosen for their large size, mobile mitochondria, and ease of visualization.
- Inducing oxidative stress using prooxidants.
- Treating yeast cells with SkQ1, a mitochondria-targeted antioxidant.
- Observing and analyzing the development of oxidative stress and mitochondrial fragmentation.
Main Results:
- Prooxidant-induced oxidative stress initiated within mitochondria, preceding generalized cellular oxidative stress.
- Findings represent the first demonstration of this phenomenon in yeast.
- SkQ1 preincubation reduced mitochondrial ROS production significantly but only slightly mitigated generalized oxidative stress.
- Mitochondrial fragmentation was primarily induced by mitochondrial ROS, occurring before widespread cellular oxidative stress.
Conclusions:
- Mitochondria are the initial sites of oxidative stress propagation within the cell.
- Mitochondrial ROS directly drives mitochondrial fragmentation.
- Yeast serves as a valuable model for studying mitochondrial dynamics and oxidative stress.
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