Researchers at the University of Vienna have delineated molecular mechanisms by which transmembrane cargo receptors initiate mitophagy, a selective autophagy process important in Parkinson’s disease pathogenesis. Their Nature Cell Biology study reveals that these receptors employ two distinct pathways to trigger autophagosome formation, differing from soluble receptors’ mechanisms, highlighting hierarchical flexibility in the autophagy machinery. This improved understanding of mitophagy initiation could inform novel treatments targeting mitochondrial dysfunction in neurodegenerative diseases.