Oligodendroglial macroautophagy is essential for myelin sheath turnover to prevent neurodegeneration and death.

ABSTRACT: Although macroautophagy deficits are implicated across adult-onset neurodegenerative diseases, we understand little about how the discrete, highly evolved cell types of the central nervous system use macroautophagy to maintain homeostasis. One such cell type is the oligodendrocyte, whose myelin sheaths are central for the reliable conduction of action potentials. Using an integrated approach of mouse genetics, live cell imaging, electron microscopy, and biochemistry, we show that mature oligodendrocytes require macroautophagy to degrade cell autonomously their myelin by consolidating cytosolic and transmembrane myelin proteins into an amphisome intermediate prior to degradation. We find that disruption of autophagic myelin turnover leads to changes in myelin sheath structure, ultimately im

SUBMITTER: Aber ER 

PROVIDER: S-EPMC9639605 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature