PA2G4/EBP1 ubiquitination by PRKN/PARKIN promotes mitophagy protecting neuron death in cerebral ischemia

Neuroprotection doesn't specify urgency, CASCADE OF DEATH does!

Will your incompetent doctor and hospital do nothing to get human testing done? NO? Then fire the whole hospital because they aren't a viable hospital.

 

PA2G4/EBP1 ubiquitination by PRKN/PARKIN promotes mitophagy protecting neuron death in cerebral ischemia

Inwoo Hwang

,

Byeong-Seong Kim

,

Ho Yun Lee

,

Sung-Woo Cho

,

Seung Eun Lee

&

Jee-Yin Ahn

Received 05 Jan 2023, Accepted 11 Sep 2023, Accepted author version posted online: 15 Sep 2023

• Cite this article
• https://doi.org/10.1080/15548627.2023.2259215
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Accepted author version

ABSTRACT

Cerebral ischemia induces massive mitochondrial damage, leading to neuronal death. The elimination of damaged mitochondria via mitophagy is critical for neuroprotection.(neuronal cascade of death is a much better term, suggesting immediacy.) Here we show that the level of PA2G4/EBP1 (proliferation-associated 2G4) was notably increased early during transient middle cerebral artery occlusion and prevented neuronal death by eliciting cerebral ischemia-reperfusion (IR)-induced mitophagy. Neuron-specific knockout of Pa2g4 increased infarct volume and aggravated neuron loss with impaired mitophagy and was rescued by introduction of adeno-associated virus serotype 2 expressing PA2G4/EBP1. We determined that PA2G4/EBP1 is ubiquitinated on lysine 376 by PRKN/PARKIN on the damaged mitochondria and interacts with receptor protein SQSTM1/p62 for mitophagy induction. Thus, our study suggests that PA2G4/EBP1 ubiquitination following cerebral IR-injury promotes mitophagy induction, which may be implicated in neuroprotection.

KEYWORDS:

• Ischemia
• mitophagy
• PA2G4/EBP1
• PRKN/PARKIN
• SQSTM1/p62

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