Ganguly 2022 MitoFit: Difference between revisions
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{{Publication | {{Publication | ||
|title=Ganguly U, Bir A, Chakrabarti S (2022) Cytotoxicity of mitochondrial Complex I inhibitor rotenone: a complex interplay of cell death pathways. 2022. | |title=Ganguly U, Bir A, Chakrabarti S (2022) Cytotoxicity of mitochondrial Complex I inhibitor rotenone: a complex interplay of cell death pathways. https://doi.org/10.26124/mitofit:2022-0013.v2 — ''2022-11-22 published in [https://doi.org//10.26124/bec:2022-0014 '''Bioenerg Commun 2022.14.''']'' | ||
|info=[[File:MitoFit Preprints pdf.png|left|160px|link=https://wiki.oroboros.at/images/6/64/Ganguly_2022_MitoFit.pdf|MitoFit pdf]] [https://wiki.oroboros.at/images/6/64/Ganguly_2022_MitoFit.pdf Cytotoxicity of mitochondrial Complex I inhibitor rotenone: a complex interplay of cell death pathways]<br/> | |info=MitoFit Preprints 2022.13.v2. [[File:MitoFit Preprints pdf.png|left|160px|link=https://wiki.oroboros.at/images/6/64/Ganguly_2022_MitoFit.pdf|MitoFit pdf]] [https://wiki.oroboros.at/images/6/64/Ganguly_2022_MitoFit.pdf Cytotoxicity of mitochondrial Complex I inhibitor rotenone: a complex interplay of cell death pathways]<br/> | ||
|authors=Ganguly Upasana, Bir Aritri, Chakrabarti Sasanka | |authors=Ganguly Upasana, Bir Aritri, Chakrabarti Sasanka | ||
|year=2022 | |year=2022 | ||
|journal=MitoFit Prep | |journal=MitoFit Prep | ||
|abstract=Ferroptosis has been identified as a type of regulated cell death triggered by a diverse set of agents with implications in various diseases like cancer and neurodegenerative diseases. Ferroptosis is iron-dependent and accompanied by an accumulation of reactive oxygen species (ROS) and lipid oxidation products, a depletion of reduced glutathione, mitochondrial morphological alterations and the rupture of cell membrane; the process is inhibited by specific antioxidants like ferrostatin-1 and liproxstatin-1 and by other general antioxidants like the iron-chelator deferoxamine, vitamin E and N-acetylcysteine. However, the mechanism of cell death in ferroptosis subsequent to the accumulation of ROS and lipid oxidation products is not clearly established. We show here that the classical mitochondrial Complex I inhibitor rotenone (0.5 µM) causes death of SH-SY5Y cells (a human neuroblastoma cell line) over a period of 48 h accompanied by mitochondrial membrane depolarization and intracellular ATP depletion. This is associated with an intracellular accumulation of ROS and the lipid oxidation product malondialdehyde or MDA and a decrease in reduced glutathione content. All these processes are inhibited very conspicuously by specific inhibitors of ferroptosis such as ferrostatin-1 and liproxstatin-1. However, the decrease in Complex I activity upon rotenone-treatment of SH-SY5Y cells is not significantly recovered by ferrostatin-1 and liproxstatin-1. When the rotenone-treated cells are analyzed morphologically by Hoechst 33258 and propidium iodide (PI) staining, a mixed picture is noticed with densely fluorescent and condensed nuclei indicating apoptotic death of cells (Hoechst 33258) and also significant numbers of necrotic cells with bright red nuclei (PI staining). | |abstract= | ||
::: <small>Version 2 ('''v2''') '''2022-11-10''' [https://wiki.oroboros.at/images/6/64/Ganguly_2022_MitoFit.pdf https://doi.org/10.26124/mitofit:2022-0013.v2]</small> | |||
::: <small>Version 1 (v1) 2022-04-19 [https://wiki.oroboros.at/images/archive/6/64/20221110103433%21Ganguly_2022_MitoFit.pdf https://doi.org/10.26124/mitofit:2022-0013]- [https://wiki.oroboros.at/index.php/File:Ganguly_2022_MitoFit.pdf »Link to all versions«]</small> | |||
Ferroptosis has been identified as a type of regulated cell death triggered by a diverse set of agents with implications in various diseases like cancer and neurodegenerative diseases. Ferroptosis is iron-dependent and accompanied by an accumulation of reactive oxygen species (ROS) and lipid oxidation products, a depletion of reduced glutathione, mitochondrial morphological alterations and the rupture of cell membrane; the process is inhibited by specific antioxidants like ferrostatin-1 and liproxstatin-1 and by other general antioxidants like the iron-chelator deferoxamine, vitamin E and N-acetylcysteine. However, the mechanism of cell death in ferroptosis subsequent to the accumulation of ROS and lipid oxidation products is not clearly established. We show here that the classical mitochondrial Complex I inhibitor rotenone (0.5 µM) causes death of SH-SY5Y cells (a human neuroblastoma cell line) over a period of 48 h accompanied by mitochondrial membrane depolarization and intracellular ATP depletion. This is associated with an intracellular accumulation of ROS and the lipid oxidation product malondialdehyde or MDA and a decrease in reduced glutathione content. All these processes are inhibited very conspicuously by specific inhibitors of ferroptosis such as ferrostatin-1 and liproxstatin-1. However, the decrease in Complex I activity upon rotenone-treatment of SH-SY5Y cells is not significantly recovered by ferrostatin-1 and liproxstatin-1. When the rotenone-treated cells are analyzed morphologically by Hoechst 33258 and propidium iodide (PI) staining, a mixed picture is noticed with densely fluorescent and condensed nuclei indicating apoptotic death of cells (Hoechst 33258) and also significant numbers of necrotic cells with bright red nuclei (PI staining). | |||
|keywords=rotenone, mitochondria, ferroptosis, reactive oxygen species, neurodegeneration | |keywords=rotenone, mitochondria, ferroptosis, reactive oxygen species, neurodegeneration | ||
|editor=[[Tindle-Solomon L]], [[Cecatto C]] | |editor=[[Tindle-Solomon L]], [[Cecatto C]] | ||
|mipnetlab=IN Haldia Chakrabarti S | |mipnetlab=IN Haldia Chakrabarti S | ||
}} | }} | ||
== Author reviewer discussion == | |||
::: [[File:MitoFit Preprints pdf.png|left|60px|link=https://wiki.oroboros.at/images/0/0c/Author_reviewer_discussions_-_Ganguly_%282022%29_MitoFit_2022.13.v2.pdf|Author reviewer dicussions pdf]] [https://wiki.oroboros.at/images/0/0c/Author_reviewer_discussions_-_Ganguly_%282022%29_MitoFit_2022.13.v2.pdf Reviewer comments leading from MitoFit Preprint version 1 to version 2] | |||
{{Labeling | {{Labeling | ||
| Line 19: | Line 24: | ||
|enzymes=Complex I, Complex III | |enzymes=Complex I, Complex III | ||
|topics=ATP production, Inhibitor, mt-Membrane potential | |topics=ATP production, Inhibitor, mt-Membrane potential | ||
|additional= | |additional= | ||
}} | }} | ||
Latest revision as of 07:47, 8 January 2023
Ganguly 2022 MitoFit
| Ganguly U, Bir A, Chakrabarti S (2022) Cytotoxicity of mitochondrial Complex I inhibitor rotenone: a complex interplay of cell death pathways. https://doi.org/10.26124/mitofit:2022-0013.v2 — 2022-11-22 published in Bioenerg Commun 2022.14. |
» MitoFit Preprints 2022.13.v2.
Ganguly Upasana, Bir Aritri, Chakrabarti Sasanka (2022) MitoFit Prep
Abstract:
- Version 2 (v2) 2022-11-10 https://doi.org/10.26124/mitofit:2022-0013.v2
- Version 1 (v1) 2022-04-19 https://doi.org/10.26124/mitofit:2022-0013- »Link to all versions«
Ferroptosis has been identified as a type of regulated cell death triggered by a diverse set of agents with implications in various diseases like cancer and neurodegenerative diseases. Ferroptosis is iron-dependent and accompanied by an accumulation of reactive oxygen species (ROS) and lipid oxidation products, a depletion of reduced glutathione, mitochondrial morphological alterations and the rupture of cell membrane; the process is inhibited by specific antioxidants like ferrostatin-1 and liproxstatin-1 and by other general antioxidants like the iron-chelator deferoxamine, vitamin E and N-acetylcysteine. However, the mechanism of cell death in ferroptosis subsequent to the accumulation of ROS and lipid oxidation products is not clearly established. We show here that the classical mitochondrial Complex I inhibitor rotenone (0.5 µM) causes death of SH-SY5Y cells (a human neuroblastoma cell line) over a period of 48 h accompanied by mitochondrial membrane depolarization and intracellular ATP depletion. This is associated with an intracellular accumulation of ROS and the lipid oxidation product malondialdehyde or MDA and a decrease in reduced glutathione content. All these processes are inhibited very conspicuously by specific inhibitors of ferroptosis such as ferrostatin-1 and liproxstatin-1. However, the decrease in Complex I activity upon rotenone-treatment of SH-SY5Y cells is not significantly recovered by ferrostatin-1 and liproxstatin-1. When the rotenone-treated cells are analyzed morphologically by Hoechst 33258 and propidium iodide (PI) staining, a mixed picture is noticed with densely fluorescent and condensed nuclei indicating apoptotic death of cells (Hoechst 33258) and also significant numbers of necrotic cells with bright red nuclei (PI staining).
• Keywords: rotenone, mitochondria, ferroptosis, reactive oxygen species, neurodegeneration • Bioblast editor: Tindle-Solomon L, Cecatto C • O2k-Network Lab: IN Haldia Chakrabarti S
Author reviewer discussion
Labels:
Pathology: Parkinson's
Stress:Cell death, Oxidative stress;RONS
Tissue;cell: Nervous system, Neuroblastoma
Enzyme: Complex I, Complex III Regulation: ATP production, Inhibitor, mt-Membrane potential
