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Spatiotemporal autophagic degradation of oxidatively damaged organelles after photodynamic stress is amplified by mitochondrial reactive oxygen species

Noemi Rubio, Isabelle Coupienne, Emmanuel Di Valentin, Ingeborg Heirman, Johan Grooten UGent, Jacques Piette and Patrizia Agostinis (2012) AUTOPHAGY. 8(9). p.1312-1324
abstract
Although reactive oxygen species (ROS) have been reported to evoke different autophagic pathways, how ROS or their secondary products modulate the selective clearance of oxidatively damaged organelles is less explored. To investigate the signaling role of ROS and the impact of their compartmentalization in autophagy pathways, we used murine fibrosarcoma L929 cells overexpressing different antioxidant enzymes targeted to the cytosol or mitochondria and subjected them to photodynamic (PD) stress with the endoplasmic reticulum (ER)-associated photosensitizer hypericin. We show that following apical ROS-mediated damage to the ER, predominantly cells overexpressing mitochondria-associated glutathione peroxidase 4 (GPX4) and manganese superoxide dismutase (SOD2) displayed attenuated kinetics of autophagosome formation and overall cell death, as detected by computerized time-lapse microscopy. Consistent with a primary ER photodamage, kinetics and colocalization studies revealed that photogenerated ROS induced an initial reticulophagy, followed by morphological changes in the mitochondrial network that preceded clearance of mitochondria by mitophagy. Overexpression of cytosolic and mitochondria-associated GPX4 retained the tubular mitochondrial network in response to PD stress and concomitantly blocked the progression toward mitophagy. Preventing the formation of phospholipid hydroperoxides and H2O2 in the cytosol as well as in the mitochondria significantly reduced cardiolipin peroxidation and apoptosis. All together, these results show that in response to apical ER photodamage ROS propagate to mitochondria, which in turn amplify ROS production, thereby contributing to two antagonizing processes, mitophagy and apoptosis.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
ROS, PDT, ER, autophagy, reticulophagy, mitophagy, apoptosis, mitochondrial ROS, HYDROPEROXIDE GLUTATHIONE-PEROXIDASE, ROS-MEDIATED MECHANISMS, CYTOCHROME-C, CELL-DEATH, CHOLESTEROL HYDROPEROXIDES, INTERMEMBRANE TRANSFER, CANCER-THERAPY, ENDOPLASMIC-RETICULUM, LIPID-PEROXIDATION, SELF-DIGESTION, photodynamic stress
journal title
AUTOPHAGY
Autophagy
volume
8
issue
9
pages
1312 - 1324
Web of Science type
Article
Web of Science id
000308634400004
JCR category
CELL BIOLOGY
JCR impact factor
12.042 (2012)
JCR rank
12/181 (2012)
JCR quartile
1 (2012)
ISSN
1554-8627
DOI
10.4161/auto.20763
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
3041819
handle
http://hdl.handle.net/1854/LU-3041819
date created
2012-11-05 09:28:21
date last changed
2012-11-05 13:39:07
@article{3041819,
  abstract     = {Although reactive oxygen species (ROS) have been reported to evoke different autophagic pathways, how ROS or their secondary products modulate the selective clearance of oxidatively damaged organelles is less explored. To investigate the signaling role of ROS and the impact of their compartmentalization in autophagy pathways, we used murine fibrosarcoma L929 cells overexpressing different antioxidant enzymes targeted to the cytosol or mitochondria and subjected them to photodynamic (PD) stress with the endoplasmic reticulum (ER)-associated photosensitizer hypericin. We show that following apical ROS-mediated damage to the ER, predominantly cells overexpressing mitochondria-associated glutathione peroxidase 4 (GPX4) and manganese superoxide dismutase (SOD2) displayed attenuated kinetics of autophagosome formation and overall cell death, as detected by computerized time-lapse microscopy. Consistent with a primary ER photodamage, kinetics and colocalization studies revealed that photogenerated ROS induced an initial reticulophagy, followed by morphological changes in the mitochondrial network that preceded clearance of mitochondria by mitophagy. Overexpression of cytosolic and mitochondria-associated GPX4 retained the tubular mitochondrial network in response to PD stress and concomitantly blocked the progression toward mitophagy. Preventing the formation of phospholipid hydroperoxides and H2O2 in the cytosol as well as in the mitochondria significantly reduced cardiolipin peroxidation and apoptosis. All together, these results show that in response to apical ER photodamage ROS propagate to mitochondria, which in turn amplify ROS production, thereby contributing to two antagonizing processes, mitophagy and apoptosis.},
  author       = {Rubio, Noemi and Coupienne, Isabelle and Di Valentin, Emmanuel and Heirman, Ingeborg and Grooten, Johan and Piette, Jacques and Agostinis, Patrizia},
  issn         = {1554-8627},
  journal      = {AUTOPHAGY},
  keyword      = {ROS,PDT,ER,autophagy,reticulophagy,mitophagy,apoptosis,mitochondrial ROS,HYDROPEROXIDE GLUTATHIONE-PEROXIDASE,ROS-MEDIATED MECHANISMS,CYTOCHROME-C,CELL-DEATH,CHOLESTEROL HYDROPEROXIDES,INTERMEMBRANE TRANSFER,CANCER-THERAPY,ENDOPLASMIC-RETICULUM,LIPID-PEROXIDATION,SELF-DIGESTION,photodynamic stress},
  language     = {eng},
  number       = {9},
  pages        = {1312--1324},
  title        = {Spatiotemporal autophagic degradation of oxidatively damaged organelles after photodynamic stress is amplified by mitochondrial reactive oxygen species},
  url          = {http://dx.doi.org/10.4161/auto.20763},
  volume       = {8},
  year         = {2012},
}

Chicago
Rubio, Noemi, Isabelle Coupienne, Emmanuel Di Valentin, Ingeborg Heirman, Johan Grooten, Jacques Piette, and Patrizia Agostinis. 2012. “Spatiotemporal Autophagic Degradation of Oxidatively Damaged Organelles After Photodynamic Stress Is Amplified by Mitochondrial Reactive Oxygen Species.” Autophagy 8 (9): 1312–1324.
APA
Rubio, N., Coupienne, I., Di Valentin, E., Heirman, I., Grooten, J., Piette, J., & Agostinis, P. (2012). Spatiotemporal autophagic degradation of oxidatively damaged organelles after photodynamic stress is amplified by mitochondrial reactive oxygen species. AUTOPHAGY, 8(9), 1312–1324.
Vancouver
1.
Rubio N, Coupienne I, Di Valentin E, Heirman I, Grooten J, Piette J, et al. Spatiotemporal autophagic degradation of oxidatively damaged organelles after photodynamic stress is amplified by mitochondrial reactive oxygen species. AUTOPHAGY. 2012;8(9):1312–24.
MLA
Rubio, Noemi, Isabelle Coupienne, Emmanuel Di Valentin, et al. “Spatiotemporal Autophagic Degradation of Oxidatively Damaged Organelles After Photodynamic Stress Is Amplified by Mitochondrial Reactive Oxygen Species.” AUTOPHAGY 8.9 (2012): 1312–1324. Print.