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bioRxiv · 10.1101/2024.05.20.594928

IP3R1 is required for meiotic progression and embryonic development by regulating mitochondrial calcium and oxidative damage

zhang, c.·Sun, Q. X.·Li, S.
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Abstract

Calcium ions (Ca2+) regulate cell proliferation and differentiation and participate in various physiological activities of cells. The calcium transfer protein inositol 1,4,5-triphosphate receptor (IP3R), located between the endoplasmic reticulum (ER) and mitochondria, plays an important role in regulating Ca2+ levels. However, the mechanism by which IP3R1 affects porcine meiotic progression and embryonic development remains unclear. We established a model in porcine oocytes using siRNA-mediated knockdown of IP3R1 to investigate the effects of IP3R1 on porcine oocyte meiotic progression and embryonic development. The results indicated that a decrease in IP3R1 expression significantly enhanced the interaction between the ER and mitochondria. Additionally, the interaction between the ER and the mitochondrial Ca2+ ([Ca2+]m) transport network protein IP3R1-GRP75-VDAC1 was disrupted. PLA decreased IP3R1, weakened the pairwise interaction between IP3R1-GRP75 and VDAC1 and significantly enhanced the interaction between GRP75 and VDAC1, resulting in the accumulation of large amounts of [Ca2+]m. These changes led to mitochondrial oxidative stress and reduced ATP production, which hindered the maturation and late development of porcine oocytes and caused apoptosis.

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zhang, c., Sun, Q. X., Li, S.. 2024-05-21. IP3R1 is required for meiotic progression and embryonic development by regulating mitochondrial calcium and oxidative damage. https://doi.org/10.1101/2024.05.20.594928

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