0598931 - BTÚ 2025 RIV NL eng J - Journal Article
Sovilj, Dana - Kelemen, Cristina D. - Dvořáková, Šárka - Zobalová, Renata - Raabová, Helena - Kriška, Ján - Heřmanová, Zuzana - Knotek, Tomáš - Anděrová, Miroslava - Klener, P. - Filimonenko, Vlada - Neužil, Jiří - Anděra, Ladislav
Cell-specific modulation of mitochondrial respiration and metabolism by the pro-apoptotic Bcl-2 family members Bax and Bak.
Apoptosis. Roč. 29, č. 3-4 (2024), s. 424-438. ISSN 1360-8185. E-ISSN 1573-675X
R&D Projects: GA ČR(CZ) GA19-08772S; GA MŠMT(CZ) LM2023050; GA MZd(CZ) NU23-03-00226; GA ČR(CZ) GA20-05942S; GA ČR(CZ) GX21-04607X; GA MZd(CZ) NU21-03-00386; GA MŠMT(CZ) EF18_046/0016045
Institutional support: RVO:86652036 ; RVO:68378041 ; RVO:68378050
Keywords : predicts poor-prognosis * endoplasmic-reticulum * complex-i * ca2+ * transcription * mcl-1
OECD category: Biochemistry and molecular biology
Impact factor: 6.1, year: 2023 ; AIS: 1.101, rok: 2023
Method of publishing: Open access
Result website:
https://link.springer.com/article/10.1007/s10495-023-01917-2#Ack1DOI: https://doi.org/10.1007/s10495-023-01917-2

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.
Permanent Link: https://hdl.handle.net/11104/0356504