AMPK and GCN2-ATF4 signal the repression of mitochondria in colon cancer cells - PubMed (original) (raw)
Comparative Study
. 2012 Jun 1;444(2):249-59.
doi: 10.1042/BJ20111829.
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- PMID: 22435535
- DOI: 10.1042/BJ20111829
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Comparative Study
AMPK and GCN2-ATF4 signal the repression of mitochondria in colon cancer cells
Inmaculada Martínez-Reyes et al. Biochem J. 2012.
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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.
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