Prostaglandin F2α regulates mitochondrial dynamics and mitophagy in the bovine corpus luteum.

Prostaglandin F2α regulates mitochondrial dynamics and mitophagy in the bovine corpus luteum.
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DOI:
10.26508/lsa.202301968
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发表时间:
2023-07
影响因子:
4.4
通讯作者:
--
中科院分区:
生物学2区
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--
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本研究探讨了前列腺素F2 α信号对牛黄体线粒体动力学和线粒体自噬的早期影响。黄体溶解介质PGF 2 α通过PKC/ERK和AMPK信号通路激活线粒体分裂并促进PINK-Parkin线粒体自噬,使线粒体成为PGF 2 α应答的新靶点。前列腺素是花生四烯酸衍生的脂质介质,参与许多生理和病理过程。PGF 2 α类似物在治疗上用于调节哺乳动物生殖周期和血压、诱导足月分娩和治疗眼部疾病。PGF 2 α通过激活Ca ~(2+)和PKC信号通路发挥作用,但对PGF 2 α信号通路所引起的细胞事件知之甚少。在这里,我们探讨了早期的影响,PGF 2 α对线粒体动力学和线粒体自噬在牛黄体采用相关的和良好的特点,在体内和体外的方法。我们确定PKC/ERK和AMPK是激活线粒体分裂蛋白DRP 1和MFF所必需的关键蛋白激酶。此外,我们还报道了PGF 2 α增加细胞内活性氧自由基,促进受体介导的PINK-Parkin线粒体自噬激活。这些发现将卵巢作为促黄体生成因子PGF 2 α的一个新靶点。了解细胞内过程中发生的早期黄体溶解可能作为一个目标,提高生育能力。
This study investigates the early effects of PGF2α signaling on mitochondrial dynamics and mitophagy in bovine corpora lutea. Luteolytic mediator PGF2α, via PKC/ERK and AMPK signaling, activates mitochondrial fission and promotes PINK–Parkin mitophagy, placing mitochondria as novel targets in response to PGF2α. Prostaglandins are arachidonic acid-derived lipid mediators involved in numerous physiological and pathological processes. PGF2α analogues are therapeutically used for regulating mammalian reproductive cycles and blood pressure, inducing term labor, and treating ocular disorders. PGF2α exerts effects via activation of calcium and PKC signaling, however, little is known about the cellular events imposed by PGF2α signaling. Here, we explored the early effects of PGF2α on mitochondrial dynamics and mitophagy in the bovine corpus luteum employing relevant and well characterized in vivo and in vitro approaches. We identified PKC/ERK and AMPK as critical protein kinases essential for activation of mitochondrial fission proteins, DRP1 and MFF. Furthermore, we report that PGF2α elicits increased intracellular reactive oxygen species and promotes receptor-mediated activation of PINK–Parkin mitophagy. These findings place the mitochondrium as a novel target in response to luteolytic mediator, PGF2α. Understanding intracellular processes occurring during early luteolysis may serve as a target for improving fertility.
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