Characterization of mitochondrial and metabolic alterations induced by trisomy 21 during neural differentiation.

ABSTRACT: Cellular redox state directs differentiation of induced pluripotent stem cells (iPSC) by energy metabolism control and ROS generation. As oxidative stress and mitochondrial dysfunction have been extensively reported in Down syndrome (DS), we evaluated mitochondrial phenotypes and energy metabolism during neural differentiation of DS iPSCs to neural progenitor cells (NPCs). Our results indicate early maturation of mitochondrial networks and elevated NADPH oxidase 4 (NOX4) expression in DS iPSCs. DS cells also fail to transition from glycolysis to oxidative phosphorylation during differentiation. Specifically, DS NPCs show an increased energetic demand that is limited in their mitochondrial and glycolytic response to mitochondrial distress. Additionally, DS iPSC and NPC non-mitochondrial oxy

SUBMITTER: Prutton KM 

PROVIDER: S-EPMC9898228 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature