Emerging evidence indicates that cell fate is pleiotropically regulated by mitochondria, which undergo specific dynamics (biogenesis, fission, fusion, and mitophagy) in the cells. In this study, we explored the possible roles of the mitochondrial dynamics (mtDYN) in neuronal and glial differentiation using in vitro models. As models, we used human-derived cell lines SH-SY and MO3.13 cells, having the potential to differentiate into neurons and oligodendrocytes (OL), respectively. First, the transcriptome analysis on the mtDYN-related genes was performed, and a common and marked increase was highlighted in the expression levels of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha) in both differentiation models.  The differentiation-related increase of PGC-1 alpha, a key regulator of mitochondrial biogenesis, was also confirmed by an immunoblot study, and interestingly, mRNA analysis suggested the protein was produced from a novel transcript variant, named OL-PCC-1 alpha. Further analyses in the OL differentiation model revealed that the mitochondrial mass was dramatically increased, and moreover, specific knockdown of OL-PGC-1 alpha resulted in a significant decrease of the mitochondrial mass and the expression OL differentiation marker proteins. Collectively, the present data at least indicate that OL-PGC-1 alpha-related mitochondria biogenesis plays promotive roles in OL differentiation, and open an avenue to study OL mtDYN in the pathophysiology underlying brain dysfunction.