TEX44-CPT1B轴调节精子中的线粒体组合和脂肪酸氧化
Erlei Zhi1, Haowei Bai1, Chuan Ren2
1Shanghai Key Laboratory of Reproductive Medicine, Department of Andrology, Department of ART, Institute of Urology, Center for Men's Health, Urologic Medical Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Nature communications
|August 23, 2025
概括
丸表达蛋白44 (TEX44) 对精子能量和运动性至关重要. 它调节脂肪酸氧化,防止氧化损伤,确保线粒体组装,从而保持男性生育能力.
科学领域:
- 生殖生物学
- 线粒体生理学
- 生物化学
背景情况:
- 线粒体脂肪酸β氧化 (FAO) 对细胞能量至关重要,但其在精子功能中的具体作用尚不清楚.
- 这种由精子运动能力受损的特征,影响男性生育能力,其潜在的分子机制需要进一步阐明.
研究的目的:
- 研究试管体表达蛋白44 (TEX44) 在精子功能中的作用及其与男性不孕症的潜在联系.
- 确定与精相关的遗传变异,并探索它们对线粒体结构和精子运动性的影响.
主要方法:
- 在800名精细体患者中进行全外体测序 (WES),以确定遗传变异.
- 产生和分析Tex44淘汰小鼠以研究其体内功能.
- 在体外生化测试以评估TEX44蛋白的活性及其与CPT1B的相互作用.
- 用于基因细胞特异性的Cpt1b淘汰小鼠模型进行比较分析.
主要成果:
- 在6名患有精的患者中发现了双性TEX44变体,与线粒体组装缺陷和精子运动性降低相关.
- TEX44充当"线粒体",与CPT1B相互作用,促进精子中的线粒体组装.
- TEX44调节了CPT1B的活性,限制了FAO和活性氧物种 (ROS) 的产生,从而防止了精子的氧化损伤.
- 在小鼠中,TEX44或Cpt1b的丧失导致类似的表型,包括线粒体缺陷和精子运动障碍.
结论:
- 通过调节脂肪酸氧化和ROS生成,TEX44对精子线粒体的完整性和功能起着至关重要的作用.
- 通过氧化应激和精子结构损伤,TEX44-CPT1B通路的失调导致男性不孕.
- 这项研究揭示了一种对男性生殖健康至关重要的新型精子特异性机制,并提供了关于精子病变的见解.
更多相关视频
相关概念视频
Porin Insertion in the Outer Mitochondrial Membrane
3.3K
Porins are beta-barrel proteins translocated to the mitochondrial outer membrane through the TOM complex into the intermembrane space. Porin precursors bind TIM chaperones within the intermembrane space and are guided to the Sorting and Assembly Machinery complex or SAM complex on the outer mitochondrial membrane.
Three models describe the assembly of porins by the SAM complex and their insertion into the outer membrane. Model 1 suggests that porins are assembled outside the SAM channel as the...
Three models describe the assembly of porins by the SAM complex and their insertion into the outer membrane. Model 1 suggests that porins are assembled outside the SAM channel as the...
3.3K
The Inner Mitochondrial Membrane
3.6K
The inner mitochondrial membrane is the primary site of ATP synthesis. The inner membrane domain that forms a smooth layer adjacent to the outer membrane is called the inner boundary membrane. This domain contains membrane transporters that drive metabolites in and out of the mitochondria. In contrast, the inner membrane network that invaginates into the matrix space is called the cristae membrane. This domain accounts for principle mitochondrial function as it accommodates the protein...
3.6K
Translocation of Proteins into the Mitochondria
3.2K
Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
3.2K
Mitochondrial Protein Sorting
4.4K
Mitochondria are double-membrane organelles of the eukaryotes involved in cellular metabolism, signaling, ATP synthesis, and programmed cell death. Each of these processes requires specific proteins and enzymes that must be correctly sorted to the right mitochondrial subcompartment for the proper functioning of the organelle.
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
4.4K
ATP Synthase: Mechanism
15.1K
In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased...
15.1K
Mitochondrial Membranes
12.3K
A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
12.3K


