Regulation of autophagy and mitophagy by nutrient availability and acetylation

• Published in: Biochimica et biophysica acta 2014-04, Vol.1841 (4), p.525-534
• Main Authors: Webster, Bradley R., Scott, Iain, Traba, Javier, Han, Kim, Sack, Michael N.
• Format: Article
• Language: English
• Subjects: Acetyl Coenzyme A - metabolism; Acetylation; Autophagy; Autophagy - genetics; Energy Metabolism; Food; GCN5L1; Humans; Mitochondria - metabolism; Mitochondrial Degradation - genetics; Mitophagy; Protein Processing, Post-Translational; Sirt3
• ISSN: 1388-1981; 0006-3002; 1879-2618
• DOI: 10.1016/j.bbalip.2014.02.001

Normal cellular function is dependent on a number of highly regulated homeostatic mechanisms, which act in concert to maintain conditions suitable for life. During periods of nutritional deficit, cells initiate a number of recycling programs which break down complex intracellular structures, thus allowing them to utilize the energy stored within. These recycling systems, broadly named “autophagy”, enable the cell to maintain the flow of nutritional substrates until they can be replenished from external sources. Recent research has shown that a number of regulatory components of the autophagy program are controlled by lysine acetylation. Lysine acetylation is a reversible post-translational modification that can alter the activity of enzymes in a number of cellular compartments. Strikingly, the main substrate for this modification is a product of cellular energy metabolism: acetyl-CoA. This suggests a direct and intricate link between fuel metabolites and the systems which regulate nutritional homeostasis. In this review, we examine how acetylation regulates the systems that control cellular autophagy, and how global protein acetylation status may act as a trigger for recycling of cellular components in a nutrient-dependent fashion. In particular, we focus on how acetylation may control the degradation and turnover of mitochondria, the major source of fuel-derived acetyl-CoA. •Nutrient levels modulate the protein acetylation.•The acetylation of proteins modifies protein function.•The autophagy and mitophagy quality control programs are regulated by acetylation.•Mitochondrial acetylation is integral in mitochondrial quality control.