The energy disruptor metformin targets mitochondrial integrity via modification of calcium flux in cancer cells
Abstract Mitochondrial integrity is critical for the regulation of cellular energy and apoptosis. Metformin is an energy disruptor targeting complex I of the respiratory chain. We demonstrate that metformin induces endoplasmic reticulum (ER) stress, calcium release from the ER and subsequent uptake...
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Nature Portfolio
2017
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oai:doaj.org-article:3c81dba573894f44b340dafd88a5e78b2021-12-02T16:06:43ZThe energy disruptor metformin targets mitochondrial integrity via modification of calcium flux in cancer cells10.1038/s41598-017-05052-22045-2322https://doaj.org/article/3c81dba573894f44b340dafd88a5e78b2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05052-2https://doaj.org/toc/2045-2322Abstract Mitochondrial integrity is critical for the regulation of cellular energy and apoptosis. Metformin is an energy disruptor targeting complex I of the respiratory chain. We demonstrate that metformin induces endoplasmic reticulum (ER) stress, calcium release from the ER and subsequent uptake of calcium into the mitochondria, thus leading to mitochondrial swelling. Metformin triggers the disorganization of the cristae and inner mitochondrial membrane in several cancer cells and tumors. Mechanistically, these alterations were found to be due to calcium entry into the mitochondria, because the swelling induced by metformin was reversed by the inhibition of mitochondrial calcium uniporter (MCU). We also demonstrated that metformin inhibits the opening of mPTP and induces mitochondrial biogenesis. Altogether, the inhibition of mPTP and the increase in mitochondrial biogenesis may account for the poor pro-apoptotic effect of metformin in cancer cells.Camille LoubiereStephan ClavelJerome GilleronRania HarissehJeremy FauconnierIssam Ben-SahraLisa KaminskiKathiane LaurentStephanie HerkenneSandra Lacas-GervaisDamien AmbrosettiDamien AlcorStephane RocchiMireille CormontJean-François MichielsBernard MariNathalie M. MazureLuca ScorranoAlain LacampagneAbdallah GharibJean-François TantiFrederic BostNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017) |
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Medicine R Science Q |
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Medicine R Science Q Camille Loubiere Stephan Clavel Jerome Gilleron Rania Harisseh Jeremy Fauconnier Issam Ben-Sahra Lisa Kaminski Kathiane Laurent Stephanie Herkenne Sandra Lacas-Gervais Damien Ambrosetti Damien Alcor Stephane Rocchi Mireille Cormont Jean-François Michiels Bernard Mari Nathalie M. Mazure Luca Scorrano Alain Lacampagne Abdallah Gharib Jean-François Tanti Frederic Bost The energy disruptor metformin targets mitochondrial integrity via modification of calcium flux in cancer cells |
| description |
Abstract Mitochondrial integrity is critical for the regulation of cellular energy and apoptosis. Metformin is an energy disruptor targeting complex I of the respiratory chain. We demonstrate that metformin induces endoplasmic reticulum (ER) stress, calcium release from the ER and subsequent uptake of calcium into the mitochondria, thus leading to mitochondrial swelling. Metformin triggers the disorganization of the cristae and inner mitochondrial membrane in several cancer cells and tumors. Mechanistically, these alterations were found to be due to calcium entry into the mitochondria, because the swelling induced by metformin was reversed by the inhibition of mitochondrial calcium uniporter (MCU). We also demonstrated that metformin inhibits the opening of mPTP and induces mitochondrial biogenesis. Altogether, the inhibition of mPTP and the increase in mitochondrial biogenesis may account for the poor pro-apoptotic effect of metformin in cancer cells. |
| format |
article |
| author |
Camille Loubiere Stephan Clavel Jerome Gilleron Rania Harisseh Jeremy Fauconnier Issam Ben-Sahra Lisa Kaminski Kathiane Laurent Stephanie Herkenne Sandra Lacas-Gervais Damien Ambrosetti Damien Alcor Stephane Rocchi Mireille Cormont Jean-François Michiels Bernard Mari Nathalie M. Mazure Luca Scorrano Alain Lacampagne Abdallah Gharib Jean-François Tanti Frederic Bost |
| author_facet |
Camille Loubiere Stephan Clavel Jerome Gilleron Rania Harisseh Jeremy Fauconnier Issam Ben-Sahra Lisa Kaminski Kathiane Laurent Stephanie Herkenne Sandra Lacas-Gervais Damien Ambrosetti Damien Alcor Stephane Rocchi Mireille Cormont Jean-François Michiels Bernard Mari Nathalie M. Mazure Luca Scorrano Alain Lacampagne Abdallah Gharib Jean-François Tanti Frederic Bost |
| author_sort |
Camille Loubiere |
| title |
The energy disruptor metformin targets mitochondrial integrity via modification of calcium flux in cancer cells |
| title_short |
The energy disruptor metformin targets mitochondrial integrity via modification of calcium flux in cancer cells |
| title_full |
The energy disruptor metformin targets mitochondrial integrity via modification of calcium flux in cancer cells |
| title_fullStr |
The energy disruptor metformin targets mitochondrial integrity via modification of calcium flux in cancer cells |
| title_full_unstemmed |
The energy disruptor metformin targets mitochondrial integrity via modification of calcium flux in cancer cells |
| title_sort |
energy disruptor metformin targets mitochondrial integrity via modification of calcium flux in cancer cells |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/3c81dba573894f44b340dafd88a5e78b |
| work_keys_str_mv |
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