Organelle quality control pathways are central to the maintenance of neuronal homeostasis. Neurons rely on basal autophagy to maintain axonal health and function, clearing synaptic vesicles and mitochondria from presynaptic sites in the distal axon. Acute damage to organelles induces more specific cellular response mechanisms leading to organelle turnover via stress-induced pathways, including lysophagy and mitophagy. We are investigating the molecular mechanisms regulating stress-induced clearance pathways in neurons and the downstream consequences of pathway dysfunction on neuronal health. Specifically, we find that lysosomal stress leads to activation of a p38 MAP kinase signaling cascade that directly affects p62-dependent lysophagy. Activation of p38MAPK and its effector kinase MK2 promotes lysophagy through phosphorylation of the small heat shock protein HSP27. Phosphorylated HSP27 localizes to damaged lysosomes via a direct interaction with the autophagy adaptor p62/SQSTM1. HSP27 recruitment maintains the fluidity of phase-separated p62 condensates that form around damaged lysosomes; liquidity of these condensates is required for efficient engulfment of the damaged organelles by autophagosomes. Mutations that disrupt these interactions inhibit lysophagy and are implicated in neurodegenerative disease. Mitophagy is also dynamically regulated; we find that increasing levels of mitochondrial stress induce a graded, proteasome-dependent response that leads to the specific degradation of negative regulators of autophagy, Rubicon and MTMR2/5. Degradation of these negative regulators increases the efficiency of PINK1/Parkin-dependent mitophagy in neurons by promoting autophagosome biogenesis and lysosomal function. Together, this work provides new insights into regulatory mechanisms modulating selective autophagy in response to organelle stress to neurons.