Are Mitochondrial Reactive Oxygen Species Required for Autophagy?
Published Date:Jul 22 2011
Source:Biochem Biophys Res Commun. 2011; 412(1):55-60.
Pubmed Central ID:PMC3171134
Funding:HL094488/HL/NHLBI NIH HHS/United States
HL70755/HL/NHLBI NIH HHS/United States
OH008282/OH/NIOSH CDC HHS/United States
R01 HL070755/HL/NHLBI NIH HHS/United States
R01 HL070755-07/HL/NHLBI NIH HHS/United States
R01 HL070755-08/HL/NHLBI NIH HHS/United States
R01 HL094488/HL/NHLBI NIH HHS/United States
R01 HL094488-01A1/HL/NHLBI NIH HHS/United States
R01 HL094488-02/HL/NHLBI NIH HHS/United States
U19 A8068021/PHS HHS/United States
U19 AI068021/AI/NIAID NIH HHS/United States
U19 AI068021-06/AI/NIAID NIH HHS/United States
U19 AI068021-07/AI/NIAID NIH HHS/United States
U19-AI068021/AI/NIAID NIH HHS/United States
Description:Reactive oxygen species (ROS) are said to participate in the autophagy signaling. Supporting evidence is obscured by interference of autophagy and apoptosis, whereby the latter heavily relies on ROS signaling. To dissect autophagy from apoptosis we knocked down expression of cytochrome c, the key component of mitochondria-dependent apoptosis, in HeLa cells using shRNA. In cytochrome c deficient HeLa1.2 cells, electron transport was compromised due to the lack of electron shuttle between mitochondrial respiratory complexes III and IV. A rapid and robust LC3-I/II conversion and mitochondria degradation were observed in HeLa1.2 cells treated with staurosporine (STS). Neither generation of superoxide nor accumulation of H(2)O(2) was detected in STS-treated HeLa1.2 cells. A membrane permeable antioxidant, PEG-SOD, plus catalase exerted no effect on STS-induced LC3-I/II conversion and mitochondria degradation. Further, STS caused autophagy in mitochondria DNA-deficient ρ° HeLa1.2 cells in which both electron transport and ROS generation were completely disrupted. Counter to the widespread view, we conclude that mitochondrial ROS are not required for the induction of autophagy.
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