Inhibition of PTEN-induced kinase 1 autophosphorylation may assist in preventing epileptogenesis induced by pentylenetetrazol

PTEN-induced kinase 1 (PINK1) autophosphorylation-triggered mitophagy is the main mitophagic pathway in the nervous system. Moreover, multiple studies have confirmed that mitophagy is closely related to the occur-rence and development of epilepsy. Therefore, we speculated that the PINK1 autophosphorylation may be involved in epileptogenesis by mediating mitophagic pathway. This study aimed to explore the contribution of activated PINK1 to epileptogenesis induced by pentylenetetrazol (PTZ) in Sprague-Dawley rats. During PTZ-induced epileptogenesis, the levels of phosphorylated PINK1 were increased, accompanied by elevated mitophagy, mitochondria oxidative stress and neuronal damage. After microRNA intervention targeting trans-locase outer mitochondrial membrane 7 (TOM7) or overlapping with the m-AAA protease 1 homolog (OMA1), the levels of PINK1 phosphorylation, mitophagy, mitochondrial oxidative stress, neuronal injury were observed in the rats with induced epileptogenesis. Furthermore, inhibiting of the expression of TOM7, a positive regulator of PINK1 autophosphorylation, reversed the increase in PINK1 phosphorylation and alleviated mitophagy, neuronal injury, thereby preventing epileptogenesis. In contrast, reducing the levels of OMA1, a negative regulator of PINK1 autophosphorylation, led to increased phosphorylation of PINK1, accompanied by aggravated neuronal injury and ultimately, epileptogenesis. This study confirmed the contribution of activated PINK1 to PTZ-induced epileptogenesis and suggested that the inhibition of PINK1 autophosphorylation may assist in preventing epileptogenesis.