PMID- 24349491
OWN - NLM
STAT- MEDLINE
DCOM- 20140929
LR  - 20220408
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 12
DP  - 2013
TI  - Mitochondrial DNA damage via augmented oxidative stress regulates endoplasmic 
      reticulum stress and autophagy: crosstalk, links and signaling.
PG  - e83349
LID - 10.1371/journal.pone.0083349 [doi]
LID - e83349
AB  - 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.
FAU - Yuzefovych, Larysa V
AU  - Yuzefovych LV
AD  - Department of Cell Biology and Neuroscience, College of Medicine, University of 
      South Alabama, Mobile, Alabama, United States of America.
FAU - LeDoux, Susan P
AU  - LeDoux SP
AD  - Department of Cell Biology and Neuroscience, College of Medicine, University of 
      South Alabama, Mobile, Alabama, United States of America.
FAU - Wilson, Glenn L
AU  - Wilson GL
AD  - Department of Cell Biology and Neuroscience, College of Medicine, University of 
      South Alabama, Mobile, Alabama, United States of America.
FAU - Rachek, Lyudmila I
AU  - Rachek LI
AD  - Department of Cell Biology and Neuroscience, College of Medicine, University of 
      South Alabama, Mobile, Alabama, United States of America.
LA  - eng
GR  - R01 DK073808/DK/NIDDK NIH HHS/United States
GR  - DK073808/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20131213
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (DNA, Mitochondrial)
SB  - IM
MH  - Animals
MH  - *Autophagy
MH  - Cell Line
MH  - *DNA Damage
MH  - DNA, Mitochondrial/*metabolism
MH  - *Endoplasmic Reticulum Stress
MH  - Humans
MH  - Mitochondria, Muscle/*metabolism/pathology
MH  - Muscle, Skeletal/*metabolism/pathology
MH  - *Oxidative Stress
MH  - Rats
MH  - *Signal Transduction
PMC - PMC3862720
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/12/19 06:00
MHDA- 2014/09/30 06:00
PMCR- 2013/12/13
CRDT- 2013/12/19 06:00
PHST- 2013/08/12 00:00 [received]
PHST- 2013/11/01 00:00 [accepted]
PHST- 2013/12/19 06:00 [entrez]
PHST- 2013/12/19 06:00 [pubmed]
PHST- 2014/09/30 06:00 [medline]
PHST- 2013/12/13 00:00 [pmc-release]
AID - PONE-D-13-32990 [pii]
AID - 10.1371/journal.pone.0083349 [doi]
PST - epublish
SO  - PLoS One. 2013 Dec 13;8(12):e83349. doi: 10.1371/journal.pone.0083349. 
      eCollection 2013.