A novel protein CYTB-187AA encoded by the mitochondrial gene CYTB modulates mammalian early development.
Cell Metab
; 36(7): 1586-1597.e7, 2024 Jul 02.
Article
in En
| MEDLINE
| ID: mdl-38703762
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cytochromes b
Limits:
Animals
/
Female
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Humans
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Male
Language:
En
Journal:
Cell Metab
Journal subject:
METABOLISMO
Year:
2024
Document type:
Article
Affiliation country:
Country of publication: