广州医科大学刘兴国团队发现，线粒体基因CYTB编码的新型蛋白质CYTB-187AA调节哺乳动物的早期发育。这一研究成果于2024年5月3日在线发表在国际学术期刊《细胞—代谢》上。

研究人员证明，细胞色素b（CYTB）是复合体III中唯一由线粒体 DNA 编码的转录本，它还使用细胞质核糖体的标准遗传密码而不是线粒体遗传密码，编码一种未被识别的长达187氨基酸的蛋白质CYTB-187AA。在利用质谱和抗体验证了这种由细胞质翻译产生的 mtDNA 编码蛋白（mPACT）的存在后，研究人员发现CYTB-187AA主要定位于线粒体基质中，并通过与溶质运载家族25成员3（SLC25A3）相互作用来调节ATP的产生，从而促进了多能状态从活化到初始的转变。

研究人员进一步建立了一个CYTB-187AA沉默的转基因敲入小鼠模型，并发现CYTB-187AA的减少会通过减少卵巢卵泡的数量而损害雌性的生育能力。研究人员首次发现了线粒体mRNA的新型mPACT模式，并证明了这种由mtDNA编码的第14种蛋白质的生理功能。

据悉，线粒体基因组转录13个mRNA，编码氧化磷酸化所必需的著名蛋白质。

附：英文原文

Title: A novel protein CYTB-187AA encoded by the mitochondrial gene CYTB modulates mammalian early development

Author: Zhijuan Hu, Liang Yang, Maolei Zhang, Haite Tang, Yile Huang, Yujie Su, Yingzhe Ding, Chong Li, Mengfei Wang, Yunhao Zhou, Qing Zhang, Liman Guo, Yue Wu, Qianqian Wang, Ning Liu, Haoran Kang, Yi Wu, Deyang Yao, Yukun Li, Zifeng Ruan, Hao Wang, Feixiang Bao, Guopan Liu, Junwei Wang, Yaofeng Wang, Wuming Wang, Gang Lu, Dajiang Qin, Duanqing Pei, Wai-Yee Chan, Xingguo Liu

Issue&Volume: 2024-05-03

Abstract: The mitochondrial genome transcribes 13 mRNAs coding for well-known proteins essentialfor oxidative phosphorylation. We demonstrate here that cytochrome b (CYTB), the only mitochondrial-DNA-encoded transcript among complex III, also encodes anunrecognized 187-amino-acid-long protein, CYTB-187AA, using the standard genetic codeof cytosolic ribosomes rather than the mitochondrial genetic code. After validatingthe existence of this mtDNA-encoded protein arising from cytosolic translation (mPACT)using mass spectrometry and antibodies, we show that CYTB-187AA is mainly localizedin the mitochondrial matrix and promotes the pluripotent state in primed-to-naivetransition by interacting with solute carrier family 25 member 3 (SLC25A3) to modulateATP production. We further generated a transgenic knockin mouse model of CYTB-187AAsilencing and found that reduction of CYTB-187AA impairs females’ fertility by decreasingthe number of ovarian follicles. For the first time, we uncovered the novel mPACTpattern of a mitochondrial mRNA and demonstrated the physiological function of this14th protein encoded by mtDNA.

DOI: 10.1016/j.cmet.2024.04.012

Source: https://www.cell.com/cell-metabolism/abstract/S1550-4131(24)00132-3