The study investigates the role of the ubiquitin kinase PINK1 in recruiting autophagy receptors to induce mitophagy. PINK1 phosphorylates ubiquitin, activating Parkin, which builds ubiquitin chains on mitochondrial outer membrane proteins. Using genome editing to knock out five autophagy receptors, the researchers found that NDP52 and Optineurin are the primary receptors for PINK1/Parkin-mediated mitophagy. PINK1 recruits NDP52 and Optineurin to mitochondria, independent of Parkin, to directly activate mitophagy. Once recruited, NDP52 and Optineurin recruit ULK1, DFCP1, and WIPI1 to focal spots near mitochondria, revealing their function upstream of LC3. This suggests that PINK1-generated phospho-ubiquitin serves as the autophagy signal on mitochondria, with Parkin amplifying it. The study also highlights the broader role of ubiquitin phosphorylation in other autophagy pathways.The study investigates the role of the ubiquitin kinase PINK1 in recruiting autophagy receptors to induce mitophagy. PINK1 phosphorylates ubiquitin, activating Parkin, which builds ubiquitin chains on mitochondrial outer membrane proteins. Using genome editing to knock out five autophagy receptors, the researchers found that NDP52 and Optineurin are the primary receptors for PINK1/Parkin-mediated mitophagy. PINK1 recruits NDP52 and Optineurin to mitochondria, independent of Parkin, to directly activate mitophagy. Once recruited, NDP52 and Optineurin recruit ULK1, DFCP1, and WIPI1 to focal spots near mitochondria, revealing their function upstream of LC3. This suggests that PINK1-generated phospho-ubiquitin serves as the autophagy signal on mitochondria, with Parkin amplifying it. The study also highlights the broader role of ubiquitin phosphorylation in other autophagy pathways.