2022年10月28日，日本京都大学
研究人员发现，精氨（SPD）可延缓各种生物体内与年龄有关的病变。补充SPD通过增加线粒体功能和激活CD8+T细胞，克服了老年小鼠对肿瘤免疫治疗的缺陷。用SPD处理初始CD8+T细胞，可急性增强脂肪酸的氧化。与珠子偶联的SPD与线粒体三功能蛋白（MTP）结合。
在从大肠杆菌合成和纯化的MTP复合物中，SPD与MTP的α和β亚单位结合，具有很强的亲和力，并异构增强了它们的酶活性。T细胞特异性缺失MTP的α亚基，取消了SPD对程序性细胞死亡蛋白1（PD-1）阻断免疫疗法的增强作用，这表明MTP是依赖SPD的T细胞激活所需的。
附：英文原文
Title: Spermidine activates mitochondrial trifunctional protein and improves antitumor immunity in mice
Author: Muna Al-Habsi, Kenji Chamoto, Ken Matsumoto, Norimichi Nomura, Baihao Zhang, Yuki Sugiura, Kazuhiro Sonomura, Aprilia Maharani, Yuka Nakajima, Yibo Wu, Yayoi Nomura, Rosemary Menzies, Masaki Tajima, Koji Kitaoka, Yasuharu Haku, Sara Delghandi, Keiko Yurimoto, Fumihiko Matsuda, So Iwata, Toshihiko Ogura, Sidonia Fagarasan, Tasuku Honjo
Issue&Volume: 2022-10-28
Abstract: Spermidine (SPD) delays age-related pathologies in various organisms. SPD supplementation overcame the impaired immunotherapy against tumors in aged mice by increasing mitochondrial function and activating CD8+ T cells. Treatment of nave CD8+ T cells with SPD acutely enhanced fatty acid oxidation. SPD conjugated to beads bound to the mitochondrial trifunctional protein (MTP). In the MTP complex, synthesized and purified from Escherichia coli, SPD bound to the α and β subunits of MTP with strong affinity and allosterically enhanced their enzymatic activities. T cell–specific deletion of the MTP α subunit abolished enhancement of programmed cell death protein 1 (PD-1) blockade immunotherapy by SPD, indicating that MTP is required for SPD-dependent T cell activation.
DOI: abj3510
Source: https://www.science.org/doi/10.1126/science.abj3510