Hyperlipidemia does not suppress mitophagy in the hippocampus. Science Communications World Wide.

Date

2024-06-01

Author

Mengi, Naz
Seker, Busranur
Kızıldag, Fulya
Onat, Umut Inci
Yanık, Tülin
Adams, Michelle

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Hyperlipidemia is a risk factor for developing atherosclerosis and neurodegenerative disorders, however, the underlying molecular mechanisms are not well understood. Protein Kinase R-like Endoplasmic Reticulum Kinase (PERK) signaling is one of the molecular pathways thought to be involved in hyperlipidemia-driven neurodegeneration. Studies indicate that mitophagy, regulated by phosphatase tension homolog-induced kinase-1 (PINK1) and Parkin, is crucial for removing damaged mitochondria; otherwise, this can lead to disrupted mitochondrial function. Increased cholesterol levels impair mitophagy in conjunction with cardiovascular disease. According to one study, lipid-induced PERK increases in Lon protease-1 (LONP1), degrades PINK1, and suppresses mitophagy in macrophages, and PERK inhibition reverses these effects. Currently, we investigated whether the brains of hyperlipidemic mice exhibit these outcomes. We evaluated the impacts of differing cholesterol levels in the hippocampus of C57BL/6 and Apoe-/- mice that were given either a western or chow diet. Inhibitors of the PERK pathway, GSK2606414, and ISRIB, were administered to western diet-fed Apoe-/- mice. Protein expression levels of LONP1, PINK1, and Parkin were examined in hippocampal mitochondrial lysates by Western blotting. Preliminary evidence showed that increased cholesterol levels, as well as inhibition of the PERK pathway, didn’t alter these markers in the hippocampus. Remarkably, this pattern differed from that observed in macrophages, implying that hyperlipidemia-induced PERK signaling might not suppress mitophagy in the hippocampus. Further analysis is being conducted to validate these findings and provide a better understanding of these inhibitors as therapeutics.

URI

https://www.world-wide.org/fens-24/hyperlipidemia-does-suppress-mitophagy-3ba17813/#:~:text=Hyperlipidemia%20does%20not%20suppress%20mitophagy%20in%20the%20hippocampus%20of%20mice,occur%20in%20the%20hippocampal%20tissue
https://hdl.handle.net/11511/111163

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Department of Biology, Article