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 ( | |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://biorxiv.org/content/early/2017/06/19/151480 '''bioRxiv Preprint''' Open Access] | |info=[http://www.bioblast.at/index.php/File:Lemieux_et_al_v-Raf-2019-05-28.pdf '''Version 2 (2019-06-11) in preparation'''], [http://biorxiv.org/content/early/2017/06/19/151480 '''bioRxiv Preprint Version 1''' Open Access] | ||
|authors=Lemieux | |authors=Lemieux Helene, Subarsky P, Doblander C, Wurm M, Troppmair J, Gnaiger Erich | ||
|year= | |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. | ||
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|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]] | ||
|mipnetlab=CA_Edmonton_Lemieux H, | |mipnetlab=CA_Edmonton_Lemieux H, AT_Innsbruck_Oroboros, AT_Innsbruck_Gnaiger E | ||
}} | }} | ||
== Preprints for Gentle Science == | |||
::::ยป [[Gentle_Science#Preprints_for_Gentle_Science |Preprints for Gentle Science]] | |||
[[Image:MITOEAGLE-logo.jpg|60px|link=http://www.mitoglobal.org/index.php/MitoEAGLE|COST Action MitoEAGLE]] In the spirit of COST Action [[WG1_MitoEAGLE_protocols,_terminology,_documentation#Documentation |MitoEAGLE WG1]] | |||
[[Image:MitoFit.jpg|60px|link=http://www.mitofit.org/index.php/K-Regio MitoFit |MitoFit]] Contribution to [[K-Regio MitoFit]] | |||
== Cited by == | |||
{{Template:Cited by Gnaiger 2020 BEC MitoPathways}} | |||
{{Labeling | {{Labeling | ||
|area=Respiration | |area=Respiration | ||
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|preparations=Intact cells, Permeabilized cells | |preparations=Intact cells, Permeabilized cells | ||
|enzymes=Complex IV;cytochrome c oxidase, Marker enzyme | |enzymes=Complex IV;cytochrome c oxidase, Marker enzyme | ||
|topics=Coupling efficiency;uncoupling, Cyt c, Flux control, Inhibitor | |topics=Coupling efficiency;uncoupling, Cyt c, Flux control, Inhibitor, Threshold;excess capacity, Uncoupler, Q-junction effect | ||
|couplingstates=LEAK, ROUTINE, OXPHOS, | |couplingstates=LEAK, ROUTINE, OXPHOS, ET | ||
|pathways=N, S, CIV, NS, ROX | |pathways=N, S, CIV, NS, ROX | ||
|instruments=Oxygraph-2k | |instruments=Oxygraph-2k | ||
|additional=MitoEAGLEPublication, BEC 2020.2 | |||
}} | }} | ||
Latest revision as of 11:08, 27 November 2021
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 (2019-06-11) in preparation, bioRxiv Preprint Version 1 Open Access
Lemieux Helene, Subarsky P, Doblander C, Wurm M, Troppmair J, Gnaiger Erich (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
Preprints for Gentle Science
In the spirit of COST Action MitoEAGLE WG1
Contribution to K-Regio MitoFit
Cited by
- Gnaiger E (2020) Mitochondrial pathways and respiratory control. An introduction to OXPHOS analysis. 5th ed. Bioenerg Commun 2020.2. https://doi.org/10.26124/bec:2020-0002
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
MitoEAGLEPublication, BEC 2020.2