Prostaglandin F2 regulates mitochondrial dynamics and mitophagy in the bovine corpus luteum

Prostaglandins are arachidonic acid-derived lipid mediators in-volved in numerous physiological and pathological processes. PGF2 alpha analogues are therapeutically used for regulating mam-malian reproductive cycles and blood pressure, inducing term labor, and treating ocular disorders. PGF2 alpha exerts effects via activation of calcium and PKC signaling, however, little is known about the cellular events imposed by PGF2 alpha signaling. Here, we explored the early effects of PGF2 alpha 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 es-sential for activation of mitochondrial fission proteins, DRP1 and MFF. Furthermore, we report that PGF2 alpha 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, PGF2 alpha. Understanding intracellular pro-cesses occurring during early luteolysis may serve as a target for improving fertility.