Considering Bypassing the Electron Transport Chain in Damaged Mitochondria

Damaged mitochondria cause problems because their electron transport chains, the core mechanism by which they generate power for the cell, stop working the right way. That leads to a situation in which sub-par mitochondria in a cell are not recycled despite being damaged, and since they replicate like bacteria the bad mitochondria take over the cell. It goes downhill from there, and this whole process is one of the fundamental causes of aging. Ways of addressing this situation include repairing the mitochondria directly or working around their damage by creating replacements for the damaged parts of mitochondrial protein machinery elsewhere in the cell. Here is another line of research that looks at trying to minimize the consequences of that damaged machinery by providing substitute components, but with a different focus: "Mitochondrial dysfunction (primary or secondary) is detrimental to intermediary metabolism. Therapeutic strategies to treat/prevent mitochondrial dysfunction could be valuable for managing metabolic and age-related disorders. Here, we review strategies proposed to treat mitochondrial impairment. We then concentrate on redox-active agents, with mild-redox potential, who shuttle electrons among specific cytosolic or mitochondrial redox-centers. We propose that specific redox agents with mild redox potential improve mitochondrial function because they can readily donate or accept electrons in biological systems, thus they enhance metabolic activity and prevent reactive oxygen species (ROS) production. These agents are likely to lack toxic effects because they lack the risk of inhibiting electron transfer in redox centers. ... This view has been demonstrated by testing the effect of several redox active agents on cellular senescence. Methylene blue (MB) appears to readily cycle between the oxidized and reduced forms using specific mitochondrial and cytosolic redox centers. MB is most effective in delaying cell senescence and enhancing mitochondrial function in vivo and in vitro. Mild-redox agents can alter the biochemical activity of specific mitochondrial components, which then in response alters the expression of nuclear and mitochondrial genes. We present the concept of mitochondrial electron-carrier bypass as a potential result of mild-redox agents, a method to prevent ROS production, improve mitochondrial function, and delay cellular aging. Thus, mild-redox agents may prevent/delay mitochondria-driven disorders."



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