(A) During autophagy, amino acids, growth factors and other signals stop activating mTOR which in turn leads to the activation of the ULK complex, the VPS34 complex and ATG9 vesicles on pre-autophagosomal regions connected to the ER and likely neighbouring phase separated assemblies (opaque circle). In the next step, VPS34 synthesises PI3P on ER-connected omegasomes which nucleate autophagosome formation by attracting the LC3 lipidation machinery. Eventually, autophagosomes separate from omegasomes and traffic to the lysosomes for degradation. (B and C) The specific ubiquitin-dependent engulfment of mitochondria during mitophagy depends on ubiquitination of mitochondrial fragments and then their association with ER strands. Engulfment is co-ordinated by mitophagy receptors (shown here for OPTN) and early autophagy proteins (shown here for ATG13) that oscillate on and off the forming mitophagosome, followed by omegasome formation (Ω) and the LC3 lipidation machinery. These sequential membrane rearrangements depend on a series of translocations of autophagy and mitophagy components to the targeted mitochondrial fragments as shown in C. Note the functional separation of FIP200 and ATG13, both components of the ULK complex. Elements of this figure have been modified from ref. [71].