Neuronal Redox-Imbalance in Rett Syndrome Affects Mitochondria as Well as Cytosol, and Is Accompanied by Intensified Mitochondrial O2 Consumption and ROS Release

Conclusion Our study confirms by quantitative subcellular redox imaging that the redox imbalance in RTT affects neurons and involves their cytosol and mitochondria. Major changes in the expression and enzyme activity of the respiratory complexes were not found, and a dissociation of mitochondrial supercomplexes was ruled out. Accordingly, massive mitochondrial defects and/or marked dysfunction of entire respiratory complexes can be excluded, which matches the observation that a pronounced neurodegeneration does not occur in RTT (Armstrong et al., 1995). Instead, only moderate alterations in mitochondrial function and/or mitochondrial regulation are to be expected, which may result in an inefficient electron flow within the respiratory chain, but do not threaten cellular viability. In line with this concept, mitochondria from Mecp2-/y hippocampus and cortex consumed more O2. This confirms the earlier proposed intensified mitochondrial respiration rates (Kriaucionis et al., 2006; Großer et al., 2012) and supports the concept that the mitochondrial underperformance in RTT may be considered an “energy wasting state” with increased O2 consumption but lowered ATP production (Jin et al., 2015). In view of these changes and the increased mitochondria mediated oxidative stress and ROS formation detected by us and others (De Filippis et al., 2015; Valenti et al., 2017), a causal chain appears more than likely. It spans from increased mitochondrial activity and O2 ...
Source: Frontiers in Physiology - Category: Physiology Source Type: research