title: Selective impairment on the proliferation of neural progenitor cells by oxidative phosphorylation disruption.
abstract: Mitochondria produce ATP, regulate apoptosis, and maintain calcium homeostasis, and thus, mitochondrial dysfunction critically impairs nervous system development. Furthermore, the disruption of oxidative phosphorylation (OXPHOS) in mitochondria could lead to energy depletion and elevate oxidative stress. In the present study, the authors investigated how perturbation of the respiratory chain and bioenergetics affects neural progenitor cells (NPCs). Mitochondrial OXPHOS was impaired by inhibiting electron transfer using the antimycin A and ATP synthase inhibitor oligomycin. It was found that oligomycin impaired NPCs proliferation and was toxic at high concentrations, whereas antimycin A-treated cells showed no changes in NPCs proliferation. Although ROS production was elevated concentration-dependently by both inhibitors, oligomycin-treated C17.2 NPCs, but not antimycin A-treated NPCs, showed a significantly higher cell death rate and lower levels of intracellular ATP. These findings suggest that bioenergetic considerations are critically important for cell viability regulation in NPCs. Taken together, the present study shows that OXPHOS disruption can have a neurotoxic effect on NPCs, and thus, adversely influence the developing brain and the neurogenic capacity of the adult brain.
authors: Department of Pharmacy, College of Pharmacy and Research Institute for Drug Development, Longevity Life Science and Technology Institutes, Pusan National University, Geumjeong-gu, Busan 609-735, Republic of Korea.
authors: Yujeong
authors: Y
authors: Lee
authors: Shin Bi
authors: SB
authors: Oh
authors: Hee Ra
authors: HR
authors: Park
authors: Hyung Sik
authors: HS
authors: Kim
authors: Min-Sun
authors: MS
authors: Kim
authors: Jaewon
authors: J
authors: Lee
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000968:Antimycin A / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation; D002531:Cerebellum / Q000166:cytology; D004734:Energy Metabolism; D051379:Mice; D025261:Mitochondrial Proton-Translocating ATPases / Q000037:antagonists & inhibitors; D058953:Neural Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009840:Oligomycins / Q000494:pharmacology; D010085:Oxidative Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D009840:Oligomycins; D017382:Reactive Oxygen Species; D000968:Antimycin A; D025261:Mitochondrial Proton-Translocating ATPases