Lemieux 2019 bioRxiv

From Bioblast
(Redirected from Lemieux 2017 bioRxiv 151480)
Jump to navigation Jump to search
Publications in the MiPMap
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 .

» 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.

Keywords: Mitochondrial respiration, OXPHOS, cytochrome c oxidase, apoptosis, CRAF, interleukin 3 Bioblast editor: Gnaiger E O2k-Network Lab: CA_Edmonton_Lemieux H, AT_Innsbruck_Oroboros, AT_Innsbruck_Gnaiger E

Preprints for Gentle Science

» Preprints for Gentle Science

COST Action MitoEAGLE In the spirit of COST Action MitoEAGLE WG1

MitoFit Contribution to K-Regio MitoFit

Cited by

Gnaiger 2020 BEC MitoPathways

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