Mitochondrial DNA Damage via Augmented Oxidative Stress Regulates Endoplasmic Reticulum Stress and Autophagy: Crosstalk, Links and SignalingReport as inadecuate




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Saturated free fatty acids FFAs have been implicated in the increase of oxidative stress, mitochondrial dysfunction, endoplasmic reticulum ER stress, autophagy, and insulin resistance IR observed in skeletal muscle. Previously, we have shown that palmitate-induced mitochondrial DNA mtDNA damage triggers mitochondrial dysfunction, mitochondrial reactive oxygen species mtROS production, apoptosis and IR in L6 myotubes. The present study showed that mitochondrial overexpression of human 8-oxoguanine DNA glycosylase-AP lyase hOGG1 decreased palmitate-induced carbonylation of proteins in mitochondria. Additionally, we found that protection of mtDNA from palmitate-induced damage significantly diminished markers of both ER stress and autophagy in L6 myotubes. Moreover, we observed that the addition of ROS scavenger, N-acetylcystein NAC, to palmitate diminished both ER stress and autophagy markers mimicking the effect of mitochondrial overexpression of hOGG1. This is the first study to show that mtDNA damage is upstream of palmitate-induced ER stress and autophagy in skeletal muscle cells.



Author: Larysa V. Yuzefovych, Susan P. LeDoux, Glenn L. Wilson, Lyudmila I. Rachek

Source: http://plos.srce.hr/



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