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Selective autophagy is a quality control system that specifically eliminates damaged or superfluous organelles, thereby maintaining cellular health. In this process, a double membrane structure called an autophagosome captures target organelles or proteins (i.e. “cargo”) and delivers the cargo to the lysosome for degradation. During the last decade, the attachment of the small protein modifier ubiquitin to cargo has emerged as a common mechanism for initiating organelle or protein capture by the autophagy machinery. In this process, a suite of ubiquitin-binding cargo receptors function to initiate autophagosome assembly in situ on the target cargo, thereby providing selectivity in cargo capture. Here we review recent efforts to understand the biochemical mechanisms and principles by which cargo are marked with ubiquitin and how ubiquitin-binding cargo receptors use conserved structural modules to recruit the autophagosome initiation machinery, with a particular focus on mitochondria and intracellular bacteria as cargo. These emerging mechanisms provide answers to long-standing questions in the field concerning how selectivity in cargo degradation is achieved to maintain cellular health. |
