Autophagy-lysosome networks in oligodendrocytes: a dynamic framework for myelin integrity

Oligodendrocytes generate and maintain myelin, a highly specialized membrane system essential for efficient signal propagation and long-term white matter integrity. The extreme biosynthetic demands and unique architecture of myelinating oligodendrocytes place exceptional pressure on intracellular quality control pathways. In this context, autophagy-lysosome networks have emerged as central regulators of oligodendrocyte biology, operating beyond bulk degradation to coordinate membrane remodeling, organelle homeostasis, and selective protein turnover. Here, we synthesize current evidence demonstrating that autophagy is dynamically regulated across the oligodendrocyte lineage and fulfills stage-specific roles, from precursor maintenance and differentiation-associated remodeling to long-term maintenance of compact myelin. We highlight advances revealing selective autophagic degradation of myelin proteins, the spatial distribution of autophagy within myelinating cells, and functional interactions between autophagy, endo-lysosomal trafficking, and myelin integrity. We also discuss emerging concepts of functional heterogeneity within autophagy-related compartments and context-dependent routing of myelin-associated cargo. Finally, we outline key open questions that define current gaps in our understanding of oligodendroglial autophagy. By framing autophagy as an integrated regulatory network rather than a single pathway, this review provides a conceptual foundation for understanding myelin biology under physiological conditions and establishes a basis for future studies on white matter vulnerability.