Real-Time Imaging of Mitochondrial ATP Dynamics Reveals the Metabolic Setting of Single Cells
Summary: Reprogramming of metabolic pathways determines cell functions and fate. In our work, we have used organelle-targeted ATP biosensors to evaluate cellular metabolic settings with high resolution in real time. Our data indicate that mitochondria dynamically supply ATP for glucose phosphorylati...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2018-10-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124718314578 |
| _version_ | 1819152134718881792 |
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| author | Maria R. Depaoli Felix Karsten Corina T. Madreiter-Sokolowski Christiane Klec Benjamin Gottschalk Helmut Bischof Emrah Eroglu Markus Waldeck-Weiermair Thomas Simmen Wolfgang F. Graier Roland Malli |
| author_facet | Maria R. Depaoli Felix Karsten Corina T. Madreiter-Sokolowski Christiane Klec Benjamin Gottschalk Helmut Bischof Emrah Eroglu Markus Waldeck-Weiermair Thomas Simmen Wolfgang F. Graier Roland Malli |
| author_sort | Maria R. Depaoli |
| collection | DOAJ |
| description | Summary: Reprogramming of metabolic pathways determines cell functions and fate. In our work, we have used organelle-targeted ATP biosensors to evaluate cellular metabolic settings with high resolution in real time. Our data indicate that mitochondria dynamically supply ATP for glucose phosphorylation in a variety of cancer cell types. This hexokinase-dependent process seems to be reversed upon the removal of glucose or other hexose sugars. Our data further verify that mitochondria in cancer cells have increased ATP consumption. Similar subcellular ATP fluxes occurred in young mouse embryonic fibroblasts (MEFs). However, pancreatic beta cells, senescent MEFs, and MEFs lacking mitofusin 2 displayed completely different mitochondrial ATP dynamics, indicative of increased oxidative phosphorylation. Our findings add perspective to the variability of the cellular bioenergetics and demonstrate that live cell imaging of mitochondrial ATP dynamics is a powerful tool to evaluate metabolic flexibility and heterogeneity at a single-cell level. : Depaoli et al. show that ATP levels, particularly within mitochondria, are affected in a highly dynamic manner by glucose depletion. Different cell types, including cancer cells, show specific mitochondrial ATP responses. These subcellular ATP signals are used to assess metabolic activity and flexibility at the single-cell level. Keywords: aerobic glycolysis, cancer cell metabolism, aging, ATP, bioenergetics, live cell imaging, mitochondria, mitofusin 2, Warburg effect, mitochondrial respiration |
| first_indexed | 2024-12-22T14:44:28Z |
| format | Article |
| id | doaj.art-16479391faa54edabaa3d109d77dcf9b |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-22T14:44:28Z |
| publishDate | 2018-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-16479391faa54edabaa3d109d77dcf9b2022-12-21T18:22:28ZengElsevierCell Reports2211-12472018-10-01252501512.e3Real-Time Imaging of Mitochondrial ATP Dynamics Reveals the Metabolic Setting of Single CellsMaria R. Depaoli0Felix Karsten1Corina T. Madreiter-Sokolowski2Christiane Klec3Benjamin Gottschalk4Helmut Bischof5Emrah Eroglu6Markus Waldeck-Weiermair7Thomas Simmen8Wolfgang F. Graier9Roland Malli10Molecular Biology and Biochemistry, Gottfried Schatz Research Center, Medical University of Graz, Neue Stiftingtalstraße 6/6, 8010 Graz, AustriaMolecular Biology and Biochemistry, Gottfried Schatz Research Center, Medical University of Graz, Neue Stiftingtalstraße 6/6, 8010 Graz, AustriaMolecular Biology and Biochemistry, Gottfried Schatz Research Center, Medical University of Graz, Neue Stiftingtalstraße 6/6, 8010 Graz, AustriaMolecular Biology and Biochemistry, Gottfried Schatz Research Center, Medical University of Graz, Neue Stiftingtalstraße 6/6, 8010 Graz, Austria; Division of Oncology, Research Unit for Long Non-coding RNAs and Genome Editing in Cancer, Medical University of Graz, Stiftingtalstraße 24, 8010 Graz, AustriaMolecular Biology and Biochemistry, Gottfried Schatz Research Center, Medical University of Graz, Neue Stiftingtalstraße 6/6, 8010 Graz, AustriaMolecular Biology and Biochemistry, Gottfried Schatz Research Center, Medical University of Graz, Neue Stiftingtalstraße 6/6, 8010 Graz, AustriaMolecular Biology and Biochemistry, Gottfried Schatz Research Center, Medical University of Graz, Neue Stiftingtalstraße 6/6, 8010 Graz, AustriaMolecular Biology and Biochemistry, Gottfried Schatz Research Center, Medical University of Graz, Neue Stiftingtalstraße 6/6, 8010 Graz, AustriaDepartment of Cell Biology, University of Alberta, Edmonton, AB T6G 2H7, CanadaMolecular Biology and Biochemistry, Gottfried Schatz Research Center, Medical University of Graz, Neue Stiftingtalstraße 6/6, 8010 Graz, Austria; BioTechMed Graz, Mozartgasse 12/II, 8010 Graz, AustriaMolecular Biology and Biochemistry, Gottfried Schatz Research Center, Medical University of Graz, Neue Stiftingtalstraße 6/6, 8010 Graz, Austria; BioTechMed Graz, Mozartgasse 12/II, 8010 Graz, Austria; Corresponding authorSummary: Reprogramming of metabolic pathways determines cell functions and fate. In our work, we have used organelle-targeted ATP biosensors to evaluate cellular metabolic settings with high resolution in real time. Our data indicate that mitochondria dynamically supply ATP for glucose phosphorylation in a variety of cancer cell types. This hexokinase-dependent process seems to be reversed upon the removal of glucose or other hexose sugars. Our data further verify that mitochondria in cancer cells have increased ATP consumption. Similar subcellular ATP fluxes occurred in young mouse embryonic fibroblasts (MEFs). However, pancreatic beta cells, senescent MEFs, and MEFs lacking mitofusin 2 displayed completely different mitochondrial ATP dynamics, indicative of increased oxidative phosphorylation. Our findings add perspective to the variability of the cellular bioenergetics and demonstrate that live cell imaging of mitochondrial ATP dynamics is a powerful tool to evaluate metabolic flexibility and heterogeneity at a single-cell level. : Depaoli et al. show that ATP levels, particularly within mitochondria, are affected in a highly dynamic manner by glucose depletion. Different cell types, including cancer cells, show specific mitochondrial ATP responses. These subcellular ATP signals are used to assess metabolic activity and flexibility at the single-cell level. Keywords: aerobic glycolysis, cancer cell metabolism, aging, ATP, bioenergetics, live cell imaging, mitochondria, mitofusin 2, Warburg effect, mitochondrial respirationhttp://www.sciencedirect.com/science/article/pii/S2211124718314578 |
| spellingShingle | Maria R. Depaoli Felix Karsten Corina T. Madreiter-Sokolowski Christiane Klec Benjamin Gottschalk Helmut Bischof Emrah Eroglu Markus Waldeck-Weiermair Thomas Simmen Wolfgang F. Graier Roland Malli Real-Time Imaging of Mitochondrial ATP Dynamics Reveals the Metabolic Setting of Single Cells Cell Reports |
| title | Real-Time Imaging of Mitochondrial ATP Dynamics Reveals the Metabolic Setting of Single Cells |
| title_full | Real-Time Imaging of Mitochondrial ATP Dynamics Reveals the Metabolic Setting of Single Cells |
| title_fullStr | Real-Time Imaging of Mitochondrial ATP Dynamics Reveals the Metabolic Setting of Single Cells |
| title_full_unstemmed | Real-Time Imaging of Mitochondrial ATP Dynamics Reveals the Metabolic Setting of Single Cells |
| title_short | Real-Time Imaging of Mitochondrial ATP Dynamics Reveals the Metabolic Setting of Single Cells |
| title_sort | real time imaging of mitochondrial atp dynamics reveals the metabolic setting of single cells |
| url | http://www.sciencedirect.com/science/article/pii/S2211124718314578 |
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