SIRT3介导CPT2去乙酰化,增强山羊颗粒细胞线粒体功能和增殖

IF 6.5 1区 农林科学 Q1 Agricultural and Biological Sciences
Shuaifei Song, Mingzhi Yang, Jiayue Li, Yaru Li, Lei Wang, Shiyi Yao, Zihan Wang, Qiuyan Li, Yanguo Han, Dejun Xu, Zhongquan Zhao
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引用次数: 0

摘要

山羊的繁殖效率与卵泡的健康发育密切相关,而卵巢颗粒细胞(GCs)的增殖在这一过程中起着至关重要的作用。Sirtuin 3 (SIRT3)是一种催化蛋白质翻译后修饰(PTMs)的酶,已知可调节多种线粒体代谢途径,从而影响细胞命运。然而,SIRT3在卵泡发育过程中的具体作用尚不清楚。因此,本研究旨在探讨SIRT3在山羊GCs线粒体功能和增殖中的调节作用及其潜在机制。在这项研究中,来自山羊卵巢小卵泡的GCs与来自大卵泡的GCs相比,具有更高的增殖潜力和SIRT3表达水平。体外,SIRT3过表达增强了GCs的线粒体功能,促进了细胞增殖,抑制了细胞凋亡。相应地,抑制SIRT3会导致相反的效果。值得注意的是,SIRT3与肉碱棕榈酰转移酶2 (CPT2)相互作用,通过介导去乙酰化来稳定CPT2蛋白,从而延长CPT2的半衰期并阻止其降解。进一步研究发现,CPT2过表达增强了GCs中脂肪酸β氧化和线粒体功能。此外,CPT2通过增加β-catenin及其下游靶点cyclin D1 (CCND1)的蛋白水平,促进了GCs的增殖。然而,这种作用被3-TYP(一种SIRT3抑制剂)逆转。SIRT3通过去乙酰化稳定CPT2蛋白的表达,从而增强山羊GCs的线粒体功能和增殖能力。这项研究为哺乳动物卵泡发育的分子机制和调控途径提供了新的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
SIRT3 mediates CPT2 delactylation to enhance mitochondrial function and proliferation in goat granulosa cells
Reproductive efficiency in goats is closely linked to the healthy development of follicles, with the proliferation of ovarian granulosa cells (GCs) playing a crucial role in this process. Sirtuin 3 (SIRT3), an enzyme that catalyzes post-translational modifications (PTMs) of proteins, is known to regulate a variety of mitochondrial metabolic pathways, thereby affecting cell fate. However, the specific effect of SIRT3 on the follicular development process remains unclear. Therefore, this study aimed to investigate the regulatory role of SIRT3 in the mitochondrial function and proliferation of goat GCs, as well as the underlying mechanisms involved. In this study, GCs from small follicles in goat ovaries presented increased proliferative potential and elevated SIRT3 expression levels compared with those from large follicles. In vitro, SIRT3 overexpression enhanced mitochondrial function, promoted proliferation and inhibited apoptosis in GCs. Correspondingly, the inhibition of SIRT3 led to the opposite effects. Notably, SIRT3 interacted with carnitine palmitoyl transferase 2 (CPT2) and stabilized the CPT2 protein by mediating delactylation, which prolonged the half-life of CPT2 and prevented its degradation. Further investigation revealed that CPT2 overexpression enhanced fatty acid β-oxidation and mitochondrial function in GCs. Additionally, CPT2 promoted the proliferation of GCs by increasing the protein levels of β-catenin and its downstream target, cyclin D1 (CCND1). However, this effect was reversed by 3-TYP (a SIRT3 inhibitor). SIRT3 stabilizes CPT2 protein expression through delactylation, thereby enhancing mitochondrial function and the proliferative capacity of GCs in goats. This study provides novel insights into the molecular mechanisms and regulatory pathways involved in mammalian follicular development.
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来源期刊
Journal of Animal Science and Biotechnology
Journal of Animal Science and Biotechnology AGRICULTURE, DAIRY & ANIMAL SCIENCE-
CiteScore
9.90
自引率
2.90%
发文量
822
审稿时长
17 weeks
期刊介绍: Journal of Animal Science and Biotechnology is an open access, peer-reviewed journal that encompasses all aspects of animal science and biotechnology. That includes domestic animal production, animal genetics and breeding, animal reproduction and physiology, animal nutrition and biochemistry, feed processing technology and bioevaluation, animal biotechnology, and meat science.
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