Macroautophagy maintains cellular homeostasis through targeting cytoplasmic 
contents and organelles into autophagosomes for degradation. This process begins 
with the assembly of protein complexes on isolation membrane to initiate the 
formation of autophagosome, followed by its nucleation, elongation and 
maturation. Fusion of autophagosomes with lysosomes then leads to degradation of 
the cargo. In the past decade, significant advances have been made on the 
identification of molecular players that are implicated in various stages of 
macroautophagy. Post-translational modifications of macroautophagy regulators 
have also been demonstrated to be critical for the selective targeting of 
cytoplasmic contents into autophagosomes. In addition, recent demonstration of 
distinct macroautophagy regulators has led to the identification of different 
subtypes of macroautophagy. Since deregulation of macroautophagy is implicated 
in diseases including neurodegenerative disorders, cancers and inflammatory 
disorders, understanding the molecular machinery of macroautophagy is crucial 
for elucidating the mechanisms by which macroautophagy is deregulated in these 
diseases, thereby revealing new potential therapeutic targets and strategies. 
Here we summarize current knowledge on the regulation of mammalian 
macroautophagy machineries and their disease-associated deregulation.