%0 Journal Article
%T A novel protein CYTB-187AA encoded by the mitochondrial gene CYTB modulates mammalian early development.
%A Hu Z
%A Yang L
%A Zhang M
%A Tang H
%A Huang Y
%A Su Y
%A Ding Y
%A Li C
%A Wang M
%A Zhou Y
%A Zhang Q
%A Guo L
%A Wu Y
%A Wang Q
%A Liu N
%A Kang H
%A Wu Y
%A Yao D
%A Li Y
%A Ruan Z
%A Wang H
%A Bao F
%A Liu G
%A Wang J
%A Wang Y
%A Wang W
%A Lu G
%A Qin D
%A Pei D
%A Chan WY
%A Liu X
%J Cell Metab
%V 36
%N 7
%D 2024 Jul 2
%M 38703762
%F 31.373
%R 10.1016/j.cmet.2024.04.012
%X The 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.