Autophagy has been predominantly studied as a nonselective self-digestion 
process that recycles macromolecules and produces energy in response to 
starvation. However, autophagy independent of nutrient status has long been 
known to exist. Recent evidence suggests that this form of autophagy enforces 
intracellular quality control by selectively disposing of aberrant protein 
aggregates and damaged organelles--common denominators in various forms of 
neurodegenerative diseases. By definition, this form of autophagy, termed 
quality-control (QC) autophagy, must be different from nutrient-regulated 
autophagy in substrate selectivity, regulation and function. We have recently 
identified the ubiquitin-binding deacetylase, HDAC6, as a key component that 
establishes QC. HDAC6 is not required for autophagy activation per se; rather, 
it is recruited to ubiquitinated autophagic substrates where it stimulates 
autophagosome-lysosome fusion by promoting F-actin remodeling in a 
cortactin-dependent manner. Remarkably, HDAC6 and cortactin are dispensable for 
starvation-induced autophagy. These findings reveal that autophagosomes 
associated with QC are molecularly and biochemically distinct from those 
associated with starvation autophagy, thereby providing a new molecular 
framework to understand the emerging complexity of autophagy and therapeutic 
potential of this unique machinery.