scholarly journals Mitochondrial complex I and cell death: a semi-automatic shotgun model

2011 ◽  
Vol 2 (10) ◽  
pp. e222-e222 ◽  
Author(s):  
D Gonzalez-Halphen ◽  
A Ghelli ◽  
L Iommarini ◽  
V Carelli ◽  
M D Esposti
Keyword(s):  
Cell Death ◽  
Complex I ◽  
Mitochondrial Complex I ◽  
Mitochondrial Complex

scholarly journals Inhibition of the ER stress IRE1α inflammatory pathway protects against cell death in mitochondrial complex I mutant cells

2018 ◽  
Vol 9 (6) ◽  
Author(s):  
Meghan S. Soustek ◽  
Eduardo Balsa ◽  
Joeva J. Barrow ◽  
Mark Jedrychowski ◽  
Rutger Vogel ◽  
...  
Keyword(s):  
Cell Death ◽  
Er Stress ◽  
Complex I ◽  
Mitochondrial Complex I ◽  
Mitochondrial Complex ◽  
Inflammatory Pathway ◽  
Mutant Cells

scholarly journals Mitochondrial Complex I Inhibitors and Forced Oxidative Phosphorylation Synergize in Inducing Cancer Cell Death

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Roberta Palorini ◽  
Tiziana Simonetto ◽  
Claudia Cirulli ◽  
Ferdinando Chiaradonna
Keyword(s):  
Cell Death ◽  
Oxidative Phosphorylation ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Complex I ◽  
Mitochondrial Complex I ◽  
Low Doses ◽  
Mitochondrial Complex ◽  
Cancer Cell Death ◽  
Glucose Depletion

Cancer cells generally rely mostly on glycolysis rather than oxidative phosphorylation (OXPHOS) for ATP production. In fact, they are particularly sensitive to glycolysis inhibition and glucose depletion. On the other hand mitochondrial dysfunctions, involved in the onset of the Warburg effect, are sometimes also associated with the resistance to apoptosis that characterizes cancer cells. Therefore, combined treatments targeting both glycolysis and mitochondria function, exploiting peculiar tumor features, might be lethal for cancer cells. In this study, we show that glucose deprivation and mitochondrial Complex I inhibitors synergize in inducing cancer cell death. In particular, our results reveal that low doses of Complex I inhibitors, ineffective on immortalized cells and in high glucose growth, become specifically cytotoxic on cancer cells deprived of glucose. Importantly, the cytotoxic effect of the inhibitors on cancer cells is strongly enhanced by forskolin, a PKA pathway activator, that we have previously shown to stimulate OXPHOS. Taken together, we demonstrate that induction in cancer cells of a switch from a glycolytic to a more respirative metabolism, obtained by glucose depletion or mitochondrial activity stimulation, strongly increases their sensitivity to low doses of mitochondrial Complex I inhibitors. Our findings might be a valuable approach to eradicate cancer cells.

Mitochondrial complex I inhibitors, acetogenins, induce HepG2 cell death through the induction of the complete apoptotic mitochondrial pathway

2012 ◽  
Vol 45 (1-2) ◽  
pp. 153-164 ◽  
Author(s):  
Nuria de Pedro ◽  
Bastien Cautain ◽  
Angeles Melguizo ◽  
Francisca Vicente ◽  
Olga Genilloud ◽  
...  
Keyword(s):  
Cell Death ◽  
Hepg2 Cell ◽  
Complex I ◽  
Mitochondrial Pathway ◽  
Mitochondrial Complex I ◽  
Mitochondrial Complex

scholarly journals Mitochondrial complex I deficiency leads to inflammation and retinal ganglion cell death in the Ndufs4 mouse

2015 ◽  
Vol 24 (10) ◽  
pp. 2848-2860 ◽  
Author(s):  
Alfred K. Yu ◽  
Lanying Song ◽  
Karl D. Murray ◽  
Deborah van der List ◽  
Chao Sun ◽  
...  
Keyword(s):  
Cell Death ◽  
Ganglion Cell ◽  
Retinal Ganglion Cell ◽  
Complex I ◽  
Mitochondrial Complex I ◽  
Retinal Ganglion ◽  
Mitochondrial Complex ◽  
Complex I Deficiency ◽  
Retinal Ganglion Cell Death ◽  
Ganglion Cell Death

scholarly journals TNF-α regulates miRNA targeting mitochondrial complex-I and induces cell death in dopaminergic cells

2015 ◽  
Vol 1852 (3) ◽  
pp. 451-461 ◽  
Author(s):  
Paresh Prajapati ◽  
Lakshmi Sripada ◽  
Kritarth Singh ◽  
Khyati Bhatelia ◽  
Rochika Singh ◽  
...  
Keyword(s):  
Cell Death ◽  
Complex I ◽  
Mitochondrial Complex I ◽  
Mitochondrial Complex ◽  
Dopaminergic Cells ◽  
Tnf Α ◽  
Mirna Targeting

scholarly journals Cell death induced by mitochondrial complex I inhibition is mediated by Iron Regulatory Protein 1

2017 ◽  
Vol 1863 (9) ◽  
pp. 2202-2209 ◽  
Author(s):  
Pamela J. Urrutia ◽  
Pabla Aguirre ◽  
Victoria Tapia ◽  
Carlos M. Carrasco ◽  
Natalia P. Mena ◽  
...  
Keyword(s):  
Cell Death ◽  
Complex I ◽  
Regulatory Protein ◽  
Mitochondrial Complex I ◽  
Iron Regulatory Protein ◽  
Mitochondrial Complex ◽  
Iron Regulatory Protein 1

scholarly journals GRIM-19, a Cell Death Regulatory Protein, Is Essential for Assembly and Function of Mitochondrial Complex I

2004 ◽  
Vol 24 (19) ◽  
pp. 8447-8456 ◽  
Author(s):  
Guochang Huang ◽  
Hao Lu ◽  
Aijun Hao ◽  
Dominic C. H. Ng ◽  
Sathivel Ponniah ◽  
...  
Keyword(s):  
Cell Death ◽  
Electron Transfer ◽  
Complex I ◽  
Cellular Localization ◽  
Regulatory Protein ◽  
Nadh:Ubiquinone Oxidoreductase ◽  
Mitochondrial Complex I ◽  
Mitochondrial Complex ◽  
Native Form

ABSTRACT Mitochondria play essential roles in cellular energy production via the oxidative phosphorylation system (OXPHOS) consisting of five multiprotein complexes and also in the initiation of apoptosis. NADH:ubiquinone oxidoreductase (complex I) is the largest complex that catalyzes the first step of electron transfer in the OXPHOS system. GRIM-19 was originally identified as a nuclear protein with apoptotic nature in interferon (IFN)- and all-trans-retinoic acid (RA)-induced tumor cells. To reveal its biological role, we generated mice deficient in GRIM-19 by gene targeting. Homologous deletion of GRIM-19 causes embryonic lethality at embryonic day 9.5. GRIM-19−/− blastocysts show retarded growth in vitro and, strikingly, display abnormal mitochondrial structure, morphology, and cellular distribution. We reexamined the cellular localization of GRIM-19 in various cell types and found its primary localization in the mitochondria. Furthermore, GRIM-19 is detected in the native form of mitochondrial complex I. Finally, we show that elimination of GRIM-19 destroys the assembly and electron transfer activity of complex I and also influences the other complexes in the mitochondrial respiratory chain. Our result demonstrates that GRIM-19, a gene product with a specific role in IFN-RA-induced cell death, is a functional component of mitochondrial complex I and is essential for early embryonic development.

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