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MOTS-c (revision 1)

Old revision·03:46, 7 Dec 2024·AnalyticalAnnie

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MOTS-c
Full nameMitochondrial open reading frame of the 12S rRNA type-c
Encoded inMitochondrial DNA
Residues16
StatusNot approved; preclinical and early human study
Compound infobox · conventions

MOTS-c is a 16-residue peptide encoded within the mitochondrial genome rather than the nuclear genome, and is one of a small group of mitochondria-derived peptides identified since the 2000s. It is not approved for any indication.[1]

Its proposed physiological role is as a signal from mitochondria to the rest of the cell and to distant tissues, influencing metabolic homeostasis. In rodent work it has been reported to improve insulin sensitivity and to protect against diet-induced obesity, through effects converging on AMP-activated protein kinase.[1]

Origin and identification

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The mitochondrial genome was long thought to encode only 13 proteins, all components of the respiratory chain. Short open reading frames within mitochondrial ribosomal RNA genes were subsequently found to encode small peptides, of which humanin was the first and MOTS-c one of the better characterised.[1]

The genomic origin has a practical consequence: mitochondrial DNA is maternally inherited and accumulates variants differently from nuclear DNA, so polymorphism in these peptides follows mitochondrial haplogroup rather than ordinary Mendelian patterns.[2]

References

  1. ^ a b c Lee C, Zeng J, Drew BG, et al. "The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance." Cell Metabolism 21(3):443–454 (2015). PMID 25738459.
  2. ^ Kim KH, Son JM, Benayoun BA, Lee C. "The mitochondrial-encoded peptide MOTS-c translocates to the nucleus to regulate nuclear gene expression in response to metabolic stress." Cell Metabolism 28(3):516–524 (2018). PMID 29983246.