A novel protein CYTB-187AA encoded by the mitochondrial gene CYTB modulates mammalian early development
Cell Metab. 2024 Apr 29:S1550-4131(24)00132-3. doi: 10.1016/j.cmet.2024.04.012. Online ahead of print.ABSTRACTThe mitochondrial genome transcribes 13 mRNAs coding for well-known proteins essential for oxidative phosphorylation. We demonstrate here that cytochrome b (CYTB), the only mitochondrial-DNA-encoded transcript among complex III, also encodes an unrecognized 187-amino-acid-long protein, CYTB-187AA, using the standard genetic code of cytosolic ribosomes rather than the mitochondrial genetic code. After validating the existence of this mtDNA-encoded protein arising from cytosolic translation (mPACT) using mass spectrometry and antibodies, we show that CYTB-187AA is mainly localized in the mitochondrial matrix and promotes the pluripotent state in primed-to-naive transition by interacting with solute carrier family 25 member 3 (SLC25A3) to modulate ATP production. We further generated a transgenic knockin mouse model of CYTB-187AA silencing and found that reduction of CYTB-187AA impairs females' fertility by decreasing the number of ovarian follicles. For the first time, we uncovered the novel mPACT pattern of a mitochondrial mRNA and demonstrated the physiological function of this 14th protein encoded by mtDNA.PMID:38703762 | DOI:10.1016/j.cmet.2024.04.012
Source: Cell Metabolism - Category: Cytology Authors: 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 W Source Type: research