Sci Rep. 2025 Apr 29. 15(1): 15078
Yi Yuan,
Xiaoqian Wang,
Yaru Cui,
Hua Zhou,
Wenna Li,
Qian Teng,
Hongjin Wang,
Bohan Sun,
Qiaoyun Wang,
Hongliu Sun,
Jianhua Tang.
This study investigated the roles and mechanisms of PINK1 activity in neonatal hypoxia-induced seizures with shRNA intervention targeting translocase outer mitochondrial membrane 7 (TOM7), the positive regulator of PINK1 autophosphorylation, or overlapping with the m-AAA protease 1 homolog (OMA1), the negative regulator of PINK1 autophosphorylation. Studies have suggested that in hypoxia-induced neonatal seizures, the phosphorylation level of PINK1 is significantly increased and the mitophagic pathway is activated, accompanied by neuronal damage and learning-memory deficits. Inhibiting PINK1 phosphorylation by reducing TOM7 expression alleviated mitophagy, mitochondrial oxidative stress, neuronal damage and seizures. In contrast, the inhibition of OMA1 expression resulted in a further increase in PINK1 phosphorylation and aggravated hypoxia-induced seizures and neuronal injury. This study implicated PINK1 activity in neonatal hypoxia and suggest that attenuated PINK1 autophosphorylation may have neuroprotective and anti-seizure effects in neonatal hypoxia.
Keywords: Mitochondrial oxidative stress; Mitophagy; Neuronal injury; PINK1; Seizure