Mitochondrial DNA damage via augmented oxidative stress regulates endoplasmic reticulum stress and autophagy: crosstalk, links and signaling

PloS One
Larysa V YuzefovychLyudmila I Rachek

Abstract

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.

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Citations

Mar 18, 2015·Molecular and Cellular Endocrinology·Ik-Rak JungYup Kang
May 16, 2015·International Journal of Molecular Medicine·Chenghu HuangShuyi Cao
Jan 16, 2015·Cell Cycle·Mauricio Menacho-MárquezJosé R Murguía
Jun 13, 2015·Journal of Ovarian Research·Perrine KafaraHubert Lincet
Sep 29, 2015·Laboratory Investigation; a Journal of Technical Methods and Pathology·Yanggang YuanChangying Xing
Jun 24, 2015·The International Journal of Biochemistry & Cell Biology·Marjolaine A Pelissier-RotaMuriel R Jacquier-Sarlin
Apr 5, 2017·Nutrients·Sho HasegawaReiko Inagi
Apr 4, 2018·Lipids in Health and Disease·Patrícia Ebersbach-SilvaUbiratan Fabres Machado
Jun 16, 2016·Oncotarget·Yanzhou YangWai Yee Chan
Mar 18, 2020·Endocrine Reviews·Alexis Diaz-VegasSergio Lavandero
Aug 18, 2018·Oxidative Medicine and Cellular Longevity·Arnold N Onyango
Nov 3, 2020·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Ryosuke TatsunamiKeisuke Sato
Jul 18, 2019·DNA Repair·Harini Sampath, R Stephen Lloyd
Nov 5, 2020·International Journal of Molecular Sciences·Adriana CelesiaSonia Emanuele
Apr 2, 2021·Journal of Theoretical Biology·Irina V DokukinaEugene A Grachev

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Methods Mentioned

BETA
light microscopy
ubiquitination

Software Mentioned

GraphPadPrism
Fujifilm Image Gauge

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