Lemieux 2019 bioRxiv: Difference between revisions
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{{Publication | {{Publication | ||
|title=Lemieux H, Subarsky P, Doblander C, Wurm M, Troppmair J, Gnaiger E (2019) Mitochondrial respiratory function as an early biomarker of apoptosis induced by growth factor removal. bioRxiv doi: https://doi.org/10.1101/151480 . | |title=Lemieux H, Subarsky P, Doblander C, Wurm M, Troppmair J, Gnaiger E (2019) Mitochondrial respiratory function as an early biomarker of apoptosis induced by growth factor removal. bioRxiv doi: https://doi.org/10.1101/151480 . | ||
|info=[http://www.bioblast.at/index.php/File:Lemieux_et_al_v-Raf-2019-05-28.pdf '''Version 2 (2019-06- | |info=[http://www.bioblast.at/index.php/File:Lemieux_et_al_v-Raf-2019-05-28.pdf '''Version 2 (2019-06-09) in preparation'''], [http://biorxiv.org/content/early/2017/06/19/151480 '''bioRxiv Preprint Version 1''' Open Access] | ||
|authors=Lemieux H, Subarsky P, Doblander C, Wurm M, Troppmair J, Gnaiger E | |authors=Lemieux H, Subarsky P, Doblander C, Wurm M, Troppmair J, Gnaiger E | ||
|year=2019 | |year=2019 | ||
|journal=bioRxiv | |journal=bioRxiv | ||
|abstract= | |abstract=Remodeling of mitochondrial metabolism is implicated in progression of cancer. Conversely, however, mitochondrial dysfunction and signaling play key roles in the induction of cell death. Apoptosis is induced following interleukin 3 (IL-3) depletion in mouse pro-myeloid 32D cells. Molecular signals of cell death are absent in 32D cells after short-term ILยญ-3 deprivation (8 h). We addressed the question if changes in mitochondrial function can be detected by high-resolution respirometry as an early event in the induction of apoptosis. Respiration of living 32D cells was suppressed by 10 to 55% following 8 h removal of IL-3, but remained more stable in 32D cells expressing the v-RAF oncogene related to CRAF. In 32D cells deprived of ILยญ3, succinate-supported respiration did not decline significantly, but respiratory capacities of the NADH-pathway and the combined NADH- and succinate-linked (NS) pathway were decreased compared to cells grown in the presence of IL-3. This was consistent with respiratory control exerted by impaired Complex IV activity, since there was not even the slightest excess Complex IV capacity above NS-pathway capacity. In contrast, electron flow reached only 60% when supported by succinate alone through Complexes II, III and IV, and was therefore relatively insensitive to Complex IV injuries up to a threshold of 40% inhibition. After IL-3 depletion respiration increased by 15% following addition of cytochrome ''c'', which provides a marker of mitochondrial outer membrane leakage, thus indicating mitochondrial fragility. Our results highlight a novel link between the key mitogenic and survival kinase CRAF and mitochondrial energy homeostasis. | ||
|keywords=Mitochondrial respiration, OXPHOS, cytochrome c oxidase, apoptosis, CRAF, interleukin 3 | |keywords=Mitochondrial respiration, OXPHOS, cytochrome c oxidase, apoptosis, CRAF, interleukin 3 | ||
|editor=[[Gnaiger E]] | |editor=[[Gnaiger E]] |
Revision as of 18:16, 9 June 2019
Lemieux H, Subarsky P, Doblander C, Wurm M, Troppmair J, Gnaiger E (2019) Mitochondrial respiratory function as an early biomarker of apoptosis induced by growth factor removal. bioRxiv doi: https://doi.org/10.1101/151480 . |
ยป Version 2 (2019-06-09) in preparation, bioRxiv Preprint Version 1 Open Access
Lemieux H, Subarsky P, Doblander C, Wurm M, Troppmair J, Gnaiger E (2019) bioRxiv
Abstract: Remodeling of mitochondrial metabolism is implicated in progression of cancer. Conversely, however, mitochondrial dysfunction and signaling play key roles in the induction of cell death. Apoptosis is induced following interleukin 3 (IL-3) depletion in mouse pro-myeloid 32D cells. Molecular signals of cell death are absent in 32D cells after short-term IL-3 deprivation (8 h). We addressed the question if changes in mitochondrial function can be detected by high-resolution respirometry as an early event in the induction of apoptosis. Respiration of living 32D cells was suppressed by 10 to 55% following 8 h removal of IL-3, but remained more stable in 32D cells expressing the v-RAF oncogene related to CRAF. In 32D cells deprived of IL3, succinate-supported respiration did not decline significantly, but respiratory capacities of the NADH-pathway and the combined NADH- and succinate-linked (NS) pathway were decreased compared to cells grown in the presence of IL-3. This was consistent with respiratory control exerted by impaired Complex IV activity, since there was not even the slightest excess Complex IV capacity above NS-pathway capacity. In contrast, electron flow reached only 60% when supported by succinate alone through Complexes II, III and IV, and was therefore relatively insensitive to Complex IV injuries up to a threshold of 40% inhibition. After IL-3 depletion respiration increased by 15% following addition of cytochrome c, which provides a marker of mitochondrial outer membrane leakage, thus indicating mitochondrial fragility. Our results highlight a novel link between the key mitogenic and survival kinase CRAF and mitochondrial energy homeostasis. โข Keywords: Mitochondrial respiration, OXPHOS, cytochrome c oxidase, apoptosis, CRAF, interleukin 3 โข Bioblast editor: Gnaiger E โข O2k-Network Lab: CA_Edmonton_Lemieux H, AT_Innsbruck_Oroboros, AT_Innsbruck_Gnaiger E
Labels: MiParea: Respiration
Pathology: Cancer
Stress:Cell death
Organism: Mouse
Tissue;cell: Blood cells
Preparation: Intact cells, Permeabilized cells
Enzyme: Complex IV;cytochrome c oxidase, Marker enzyme
Regulation: Coupling efficiency;uncoupling, Cyt c, Flux control, Inhibitor, Threshold;excess capacity, Uncoupler, Q-junction effect
Coupling state: LEAK, ROUTINE, OXPHOS, ET
Pathway: N, S, CIV, NS, ROX
HRR: Oxygraph-2k
Preprints for Gentle Science
In the spirit of COST Action MitoEAGLE WG1
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