scholarly journals Overexpression of Lon contributes to survival and aggressive phenotype of cancer cells through mitochondrial complex I-mediated generation of reactive oxygen species

2013 ◽  
Vol 4 (6) ◽  
pp. e681-e681 ◽  
Author(s):  
C-W Cheng ◽  
C-Y Kuo ◽  
C-C Fan ◽  
W-C Fang ◽  
S S Jiang ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cancer Cells ◽  
Complex I ◽  
Reactive Oxygen ◽  
Mitochondrial Complex I ◽  
Oxygen Species ◽  
Mitochondrial Complex ◽  
Aggressive Phenotype

scholarly journals Metabolic determinants of cellular fitness dependent on mitochondrial reactive oxygen species

2020 ◽  
Vol 6 (45) ◽  
pp. eabb7272
Author(s):  
Hyewon Kong ◽  
Colleen R. Reczek ◽  
Gregory S. McElroy ◽  
Elizabeth M. Steinert ◽  
Tim Wang ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cancer Cells ◽  
Complex I ◽  
Lymphoblastic Leukemia ◽  
Reactive Oxygen ◽  
Complex Iii ◽  
Mitochondrial Complex I ◽  
Oxygen Species ◽  
Mitochondrial Complex

Mitochondria-derived reactive oxygen species (mROS) are required for the survival, proliferation, and metastasis of cancer cells. The mechanism by which mitochondrial metabolism regulates mROS levels to support cancer cells is not fully understood. To address this, we conducted a metabolism-focused CRISPR-Cas9 genetic screen and uncovered that loss of genes encoding subunits of mitochondrial complex I was deleterious in the presence of the mitochondria-targeted antioxidant mito-vitamin E (MVE). Genetic or pharmacologic inhibition of mitochondrial complex I in combination with the mitochondria-targeted antioxidants, MVE or MitoTEMPO, induced a robust integrated stress response (ISR) and markedly diminished cell survival and proliferation in vitro. This was not observed following inhibition of mitochondrial complex III. Administration of MitoTEMPO in combination with the mitochondrial complex I inhibitor phenformin decreased the leukemic burden in a mouse model of T cell acute lymphoblastic leukemia. Thus, mitochondrial complex I is a dominant metabolic determinant of mROS-dependent cellular fitness.

scholarly journals The Putative Drp1 Inhibitor mdivi-1 Is a Reversible Mitochondrial Complex I Inhibitor that Modulates Reactive Oxygen Species

2017 ◽  
Vol 40 (6) ◽  
pp. 583-594.e6 ◽  
Author(s):  
Evan A. Bordt ◽  
Pascaline Clerc ◽  
Brian A. Roelofs ◽  
Andrew J. Saladino ◽  
László Tretter ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Complex I ◽  
Reactive Oxygen ◽  
Mitochondrial Complex I ◽  
Oxygen Species ◽  
Mitochondrial Complex ◽  
Mitochondrial Complex I Inhibitor

Fluazinam targets mitochondrial complex I to induce reactive oxygen species-dependent cytotoxicity in SH-SY5Y cells

2012 ◽  
Vol 60 (8) ◽  
pp. 773-781 ◽  
Author(s):  
Jeong Eun Lee ◽  
Jin Sun Kang ◽  
Yeo-Woon Ki ◽  
Jae Hyeon Park ◽  
In Chul Shin ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Complex I ◽  
Reactive Oxygen ◽  
Mitochondrial Complex I ◽  
Oxygen Species ◽  
Mitochondrial Complex

scholarly journals Physiologic Implications of Reactive Oxygen Species Production by Mitochondrial Complex I Reverse Electron Transport

Antioxidants ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 285 ◽  
Author(s):  
John O. Onukwufor ◽  
Brandon J. Berry ◽  
Andrew P. Wojtovich
Keyword(s):  
Reactive Oxygen Species ◽  
Electron Transport ◽  
Complex I ◽  
Reactive Oxygen ◽  
Reverse Direction ◽  
Mitochondrial Complex I ◽  
Ros Production ◽  
Oxygen Species ◽  
Mitochondrial Complex ◽  
Reverse Electron Transport

Mitochondrial reactive oxygen species (ROS) can be either detrimental or beneficial depending on the amount, duration, and location of their production. Mitochondrial complex I is a component of the electron transport chain and transfers electrons from NADH to ubiquinone. Complex I is also a source of ROS production. Under certain thermodynamic conditions, electron transfer can reverse direction and reduce oxygen at complex I to generate ROS. Conditions that favor this reverse electron transport (RET) include highly reduced ubiquinone pools, high mitochondrial membrane potential, and accumulated metabolic substrates. Historically, complex I RET was associated with pathological conditions, causing oxidative stress. However, recent evidence suggests that ROS generation by complex I RET contributes to signaling events in cells and organisms. Collectively, these studies demonstrate that the impact of complex I RET, either beneficial or detrimental, can be determined by the timing and quantity of ROS production. In this article we review the role of site-specific ROS production at complex I in the contexts of pathology and physiologic signaling.

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