{Reference Type}: Journal Article
{Title}: A novel protein CYTB-187AA encoded by the mitochondrial gene CYTB modulates mammalian early development.
{Author}: Hu Z;Yang L;Zhang M;Tang H;Huang Y;Su Y;Ding Y;Li C;Wang M;Zhou Y;Zhang Q;Guo L;Wu Y;Wang Q;Liu N;Kang H;Wu Y;Yao D;Li Y;Ruan Z;Wang H;Bao F;Liu G;Wang J;Wang Y;Wang W;Lu G;Qin D;Pei D;Chan WY;Liu X;
{Journal}: Cell Metab
{Volume}: 36
{Issue}: 7
{Year}: 2024 Jul 2
{Factor}: 31.373
{DOI}: 10.1016/j.cmet.2024.04.012
{Abstract}: 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.