Mitochondrial network reorganization and transient expansion during oligodendrocyte generation

ABSTRACT Oligodendrocyte precursor cells (OPCs) give rise to myelinating oligodendrocytes of the central nervous system. This process persists throughout life and is essential for recovery from neurodegeneration. To better understand the cellular checkpoints that occur during oligodendrogenesis, we determined the mitochondrial distribution and morphometrics across the oligodendrocyte lineage in mouse and human cerebral cortex. During oligodendrocyte generation, mitochondrial content expanded concurrently with a change in subcellular partitioning towards the distal processes. These changes were followed by an abrupt loss of mitochondria in the oligodendrocyte processes and myelin, coinciding with sheath compaction. This reorganization and extensive expansion and depletion took 3 days. Oligodendrocyte mitochondria were stationary over days while OPC mitochondrial motility was modulated by animal arousal state within minutes. Aged OPCs also displayed decreased mitochondrial size, content, and motility. Thus, mitochondrial dynamics are linked to oligodendrocyte generation, dynamically modified by their local microenvironment, and altered in the aging brain.