Cargando…
Specific Features of Mitochondrial Dysfunction under Conditions of Ferroptosis Induced by t-Butylhydroperoxide and Iron: Protective Role of the Inhibitors of Lipid Peroxidation and Mitochondrial Permeability Transition Pore Opening
Recent studies have indicated the critical importance of mitochondria in the induction and progression of ferroptosis. There is evidence indicating that tert-butyl hydroperoxide (TBH), a lipid-soluble organic peroxide, is capable of inducing ferroptosis-type cell death. We investigated the effect of...
Autores principales: | , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10145271/ https://www.ncbi.nlm.nih.gov/pubmed/37103799 http://dx.doi.org/10.3390/membranes13040372 |
_version_ | 1785034293531115520 |
---|---|
author | Fedotcheva, Tatiana Shimanovsky, Nikolai Fedotcheva, Nadezhda |
author_facet | Fedotcheva, Tatiana Shimanovsky, Nikolai Fedotcheva, Nadezhda |
author_sort | Fedotcheva, Tatiana |
collection | PubMed |
description | Recent studies have indicated the critical importance of mitochondria in the induction and progression of ferroptosis. There is evidence indicating that tert-butyl hydroperoxide (TBH), a lipid-soluble organic peroxide, is capable of inducing ferroptosis-type cell death. We investigated the effect of TBH on the induction of nonspecific membrane permeability measured by mitochondrial swelling and on oxidative phosphorylation and NADH oxidation assessed by NADH fluo rescence. TBH and iron, as well as their combinations, induced, with a respective decrease in the lag phase, the swelling of mitochondria, inhibited oxidative phosphorylation and stimulated NADH oxidation. The lipid radical scavenger butylhydroxytoluene (BHT), the inhibitor of mitochondrial phospholipase iPLA2γ bromoenol lactone (BEL), and the inhibitor of the mitochondrial permeability transition pore (MPTP) opening cyclosporine A (CsA) were equally effective in protecting these mitochondrial functions. The radical-trapping antioxidant ferrostatin-1, a known indicator of ferroptotic alteration, restricted the swelling but was less effective than BHT. ADP and oligomycin significantly decelerated iron- and TBH-induced swelling, confirming the involvement of MPTP opening in mitochondrial dysfunction. Thus, our data showed the participation of phospholipase activation, lipid peroxidation, and the MPTP opening in the mitochondria-dependent ferroptosis. Presumably, their involvement took place at different stages of membrane damage initiated by ferroptotic stimuli. |
format | Online Article Text |
id | pubmed-10145271 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-101452712023-04-29 Specific Features of Mitochondrial Dysfunction under Conditions of Ferroptosis Induced by t-Butylhydroperoxide and Iron: Protective Role of the Inhibitors of Lipid Peroxidation and Mitochondrial Permeability Transition Pore Opening Fedotcheva, Tatiana Shimanovsky, Nikolai Fedotcheva, Nadezhda Membranes (Basel) Article Recent studies have indicated the critical importance of mitochondria in the induction and progression of ferroptosis. There is evidence indicating that tert-butyl hydroperoxide (TBH), a lipid-soluble organic peroxide, is capable of inducing ferroptosis-type cell death. We investigated the effect of TBH on the induction of nonspecific membrane permeability measured by mitochondrial swelling and on oxidative phosphorylation and NADH oxidation assessed by NADH fluo rescence. TBH and iron, as well as their combinations, induced, with a respective decrease in the lag phase, the swelling of mitochondria, inhibited oxidative phosphorylation and stimulated NADH oxidation. The lipid radical scavenger butylhydroxytoluene (BHT), the inhibitor of mitochondrial phospholipase iPLA2γ bromoenol lactone (BEL), and the inhibitor of the mitochondrial permeability transition pore (MPTP) opening cyclosporine A (CsA) were equally effective in protecting these mitochondrial functions. The radical-trapping antioxidant ferrostatin-1, a known indicator of ferroptotic alteration, restricted the swelling but was less effective than BHT. ADP and oligomycin significantly decelerated iron- and TBH-induced swelling, confirming the involvement of MPTP opening in mitochondrial dysfunction. Thus, our data showed the participation of phospholipase activation, lipid peroxidation, and the MPTP opening in the mitochondria-dependent ferroptosis. Presumably, their involvement took place at different stages of membrane damage initiated by ferroptotic stimuli. MDPI 2023-03-24 /pmc/articles/PMC10145271/ /pubmed/37103799 http://dx.doi.org/10.3390/membranes13040372 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Fedotcheva, Tatiana Shimanovsky, Nikolai Fedotcheva, Nadezhda Specific Features of Mitochondrial Dysfunction under Conditions of Ferroptosis Induced by t-Butylhydroperoxide and Iron: Protective Role of the Inhibitors of Lipid Peroxidation and Mitochondrial Permeability Transition Pore Opening |
title | Specific Features of Mitochondrial Dysfunction under Conditions of Ferroptosis Induced by t-Butylhydroperoxide and Iron: Protective Role of the Inhibitors of Lipid Peroxidation and Mitochondrial Permeability Transition Pore Opening |
title_full | Specific Features of Mitochondrial Dysfunction under Conditions of Ferroptosis Induced by t-Butylhydroperoxide and Iron: Protective Role of the Inhibitors of Lipid Peroxidation and Mitochondrial Permeability Transition Pore Opening |
title_fullStr | Specific Features of Mitochondrial Dysfunction under Conditions of Ferroptosis Induced by t-Butylhydroperoxide and Iron: Protective Role of the Inhibitors of Lipid Peroxidation and Mitochondrial Permeability Transition Pore Opening |
title_full_unstemmed | Specific Features of Mitochondrial Dysfunction under Conditions of Ferroptosis Induced by t-Butylhydroperoxide and Iron: Protective Role of the Inhibitors of Lipid Peroxidation and Mitochondrial Permeability Transition Pore Opening |
title_short | Specific Features of Mitochondrial Dysfunction under Conditions of Ferroptosis Induced by t-Butylhydroperoxide and Iron: Protective Role of the Inhibitors of Lipid Peroxidation and Mitochondrial Permeability Transition Pore Opening |
title_sort | specific features of mitochondrial dysfunction under conditions of ferroptosis induced by t-butylhydroperoxide and iron: protective role of the inhibitors of lipid peroxidation and mitochondrial permeability transition pore opening |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10145271/ https://www.ncbi.nlm.nih.gov/pubmed/37103799 http://dx.doi.org/10.3390/membranes13040372 |
work_keys_str_mv | AT fedotchevatatiana specificfeaturesofmitochondrialdysfunctionunderconditionsofferroptosisinducedbytbutylhydroperoxideandironprotectiveroleoftheinhibitorsoflipidperoxidationandmitochondrialpermeabilitytransitionporeopening AT shimanovskynikolai specificfeaturesofmitochondrialdysfunctionunderconditionsofferroptosisinducedbytbutylhydroperoxideandironprotectiveroleoftheinhibitorsoflipidperoxidationandmitochondrialpermeabilitytransitionporeopening AT fedotchevanadezhda specificfeaturesofmitochondrialdysfunctionunderconditionsofferroptosisinducedbytbutylhydroperoxideandironprotectiveroleoftheinhibitorsoflipidperoxidationandmitochondrialpermeabilitytransitionporeopening |