AMPK and GCN2-ATF4 signal the repression of mitochondria in colon cancer cells
- PMID: 22435535
- DOI: 10.1042/BJ20111829
AMPK and GCN2-ATF4 signal the repression of mitochondria in colon cancer cells
Abstract
Reprogramming of energetic metabolism is a phenotypic trait of cancer in which mitochondrial dysfunction represents a key event in tumour progression. In the present study, we show that the acquisition of the tumour-promoting phenotype in colon cancer HCT116 cells treated with oligomycin to inhibit ATP synthase is exerted by repression of the synthesis of nuclear-encoded mitochondrial proteins in a process that is regulated at the level of translation. Remarkably, the synthesis of glycolytic proteins is not affected in this situation. Changes in translational control of mitochondrial proteins are signalled by the activation of AMPK (AMP-activated protein kinase) and the GCN2 (general control non-derepressible 2) kinase, leading also to the activation of autophagy. Changes in the bioenergetic function of mitochondria are mimicked by the activation of AMPK and the silencing of ATF4 (activating transcription factor 4). These findings emphasize the relevance of translational control for normal mitochondrial function and for the progression of cancer. Moreover, they demonstrate that glycolysis and oxidative phosphorylation are controlled at different levels of gene expression, offering the cell a mechanistic safeguard strategy for metabolic adaptation under stressful conditions.
Similar articles
-
Redox implications of AMPK-mediated signal transduction beyond energetic clues.J Cell Sci. 2012 May 1;125(Pt 9):2115-25. doi: 10.1242/jcs.095216. Epub 2012 May 22. J Cell Sci. 2012. PMID: 22619229 Review.
-
Involvement of AMPK signaling cascade in capsaicin-induced apoptosis of HT-29 colon cancer cells.Ann N Y Acad Sci. 2007 Jan;1095:496-503. doi: 10.1196/annals.1397.053. Ann N Y Acad Sci. 2007. PMID: 17404062
-
Selenium regulates cyclooxygenase-2 and extracellular signal-regulated kinase signaling pathways by activating AMP-activated protein kinase in colon cancer cells.Cancer Res. 2006 Oct 15;66(20):10057-63. doi: 10.1158/0008-5472.CAN-06-1814. Cancer Res. 2006. PMID: 17047069
-
AMPK-mediated regulation of transcription in skeletal muscle.Clin Sci (Lond). 2010 Jan 26;118(8):507-18. doi: 10.1042/CS20090533. Clin Sci (Lond). 2010. PMID: 20088830 Review.
-
Regulation of autophagy by ATF4 in response to severe hypoxia.Oncogene. 2010 Aug 5;29(31):4424-35. doi: 10.1038/onc.2010.191. Epub 2010 May 31. Oncogene. 2010. PMID: 20514020
Cited by
-
Mitochondrial translation is the primary determinant of secondary mitochondrial complex I deficiencies.iScience. 2024 Jul 19;27(8):110560. doi: 10.1016/j.isci.2024.110560. eCollection 2024 Aug 16. iScience. 2024. PMID: 39184436 Free PMC article.
-
Multifaceted role of GCN2 in tumor adaptation and therapeutic targeting.Transl Oncol. 2024 Nov;49:102096. doi: 10.1016/j.tranon.2024.102096. Epub 2024 Aug 22. Transl Oncol. 2024. PMID: 39178574 Free PMC article. Review.
-
PKR Mediates the Mitochondrial Unfolded Protein Response through Double-Stranded RNA Accumulation under Mitochondrial Stress.Int J Mol Sci. 2024 Jul 15;25(14):7738. doi: 10.3390/ijms25147738. Int J Mol Sci. 2024. PMID: 39062980 Free PMC article.
-
The GCN2/eIF2αK stress kinase regulates PP1 to ensure mitotic fidelity.EMBO Rep. 2023 Aug 3;24(8):e56100. doi: 10.15252/embr.202256100. Epub 2023 Jun 9. EMBO Rep. 2023. PMID: 37291955 Free PMC article.
-
F1Fo adenosine triphosphate (ATP) synthase is a potential drug target in non-communicable diseases.Mol Biol Rep. 2023 Apr;50(4):3849-3862. doi: 10.1007/s11033-023-08299-3. Epub 2023 Jan 30. Mol Biol Rep. 2023. PMID: 36715790 Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
