Selective autophagy receptors: Multifunctional regulators of organelle turnover

Organelle-selective autophagy (organellophagy) is essential for organelle quality control and cellular homeostasis. Selective degradation of most major organelles has been described and is mediated by specialized autophagy receptors. These receptors were initially defined by their ability to tether target substrates to the growing phagophore through interactions between their LC3-interacting region (LIR) motifs and ATG8 family proteins. Recent studies have expanded this view, revealing that autophagy receptors function as multifunctional regulators. Beyond substrate recognition, they have been shown to promote local concentration of substrates and autophagy factors via liquid-liquid phase separation, actively drive fragmentation of large organelles into autophagosome-compatible sizes, and recruit the autophagy initiation machinery. Together, these findings refine current models of organellophagy and highlight autophagy receptors as central coordinators of organelle turnover.