Cell-specific modulation of mitochondrial respiration and metabolism by the pro-apoptotic Bcl-2 family members Bax and Bak.

Autor: Sovilj D; Institute of Biotechnology, Czech Academy of Sciences, Vestec, Prague, Czech Republic., Kelemen CD; Institute of Biotechnology, Czech Academy of Sciences, Vestec, Prague, Czech Republic.; Faculty of Science, Charles University, Prague, Czech Republic., Dvorakova S; Institute of Biotechnology, Czech Academy of Sciences, Vestec, Prague, Czech Republic., Zobalova R; Institute of Biotechnology, Czech Academy of Sciences, Vestec, Prague, Czech Republic., Raabova H; Institute of Molecular Genetics, Czech Academy of Sciences, Prague, Czech Republic., Kriska J; Institute of Experimental Medicine, Czech Academy of Sciences, Prague, Czech Republic., Hermanova Z; Institute of Experimental Medicine, Czech Academy of Sciences, Prague, Czech Republic., Knotek T; Institute of Experimental Medicine, Czech Academy of Sciences, Prague, Czech Republic., Anderova M; Institute of Experimental Medicine, Czech Academy of Sciences, Prague, Czech Republic., Klener P; First Faculty of Medicine, Institute of Pathological Physiology, Charles University, Prague, Czech Republic., Filimonenko V; Institute of Molecular Genetics, Czech Academy of Sciences, Prague, Czech Republic., Neuzil J; Institute of Biotechnology, Czech Academy of Sciences, Vestec, Prague, Czech Republic.; Faculty of Science, Charles University, Prague, Czech Republic.; First Faculty of Medicine, Charles University, Prague, Czech Republic.; School of Pharmacy and Medical Science, Griffith University, Southport, QLD, Australia., Andera L; Institute of Biotechnology, Czech Academy of Sciences, Vestec, Prague, Czech Republic. Ladislav.andera@ibt.cas.cz.; Institute of Molecular Genetics, Czech Academy of Sciences, Prague, Czech Republic. Ladislav.andera@ibt.cas.cz.
Jazyk: angličtina
Zdroj: Apoptosis : an international journal on programmed cell death [Apoptosis] 2024 Apr; Vol. 29 (3-4), pp. 424-438. Date of Electronic Publication: 2023 Nov 24.
DOI: 10.1007/s10495-023-01917-2
Abstrakt: Proteins from the Bcl-2 family play an essential role in the regulation of apoptosis. However, they also possess cell death-unrelated activities that are less well understood. This prompted us to study apoptosis-unrelated activities of the Bax and Bak, pro-apoptotic members of the Bcl-2 family. We prepared Bax/Bak-deficient human cancer cells of different origin and found that while respiration in the glioblastoma U87 Bax/Bak-deficient cells was greatly enhanced, respiration of Bax/Bak-deficient B lymphoma HBL-2 cells was slightly suppressed. Bax/Bak-deficient U87 cells also proliferated faster in culture, formed tumours more rapidly in mice, and showed modulation of metabolism with a considerably increased NAD + /NADH ratio. Follow-up analyses documented increased/decreased expression of mitochondria-encoded subunits of respiratory complexes and stabilization/destabilization of the mitochondrial transcription elongation factor TEFM in Bax/Bak-deficient U87 and HBL-2 cells, respectively. TEFM downregulation using shRNAs attenuated mitochondrial respiration in Bax/Bak-deficient U87 as well as in parental HBL-2 cells. We propose that (post)translational regulation of TEFM levels in Bax/Bak-deficient cells modulates levels of subunits of mitochondrial respiratory complexes that, in turn, contribute to respiration and the accompanying changes in metabolism and proliferation in these cells.
(© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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