Cell growth on autophagy

Effects of cell growth on autophagy. Growth-dependent import of nutrients, such as amino acids and glucose, generates multiple signals that influence the induction of autophagy through their effects on pH, osmotic pressure (Π) and the electrochemical gradient (ΔΨ), as well as through several key signaling molecules such as Gcn2 (EIF2AK4 in mammals), TOR (or mTOR) and AMPK. The eIF2α kinase Gcn2 senses reduced amino acid levels through the accumulation of uncharged tRNAs, and activates autophagy-related gene expression through the transcription factor Gcn4 (ATG4 in mammals). Amino acids activate the mTOR pathway, in part, by recruiting mTOR complexes to the lysosomal surface through factors such as the Rag GTPases and p62, and through effects on intracellular lysosomal positioning. The AMP-activated protein kinase (AMPK) responds to glucose uptake, and regulates multiple downstream targets that have effects on autophagy, including mTOR, Atg1 (ULK1 in mammals) and CDKs (through cyclin kinase inhibitors; CKIs). The induction of autophagy can also be suppressed by the presence of actively translating ribosomes on the surface of the endoplasmic reticulum, which might limit the availability of sites for autophagosome nucleation. Additional components of TOR, Atg1 and Vps34 complexes are indicated. Please refer to the text for details.

Publication

Autophagy and cell growth – the yin and yang of nutrient responses. (2012) Thomas P. Neufeld. J Cell Sci. 2012 May 15;125(10):2359-2368. Figure: F3. All organisms Drosophila melanogaster Danio rerio Caenorhabditis elegans Arabidopsis thaliana Homo sapiens

Disease mentions