BioAcyl Corp
BioAcyl Corp |
|
 |
 |
 |
|
Yong, C. Q. Y., & Tang, B. L. (2018). A mitochondrial encoded messenger at the nucleus. Cells, 7(105). Added by: Dr. Enrique Feoli (31/03/2026, 19:55) Last edited by: Dr. Enrique Feoli (31/03/2026, 19:58) |
 |
| Resource type: Journal Article DOI: 10.3390/cells7080105 ID no. (ISBN etc.): 2073-4409 BibTeX citation key: Yong2018 View all bibliographic details  |
Categories: BioAcyl Corp Subcategories: MOTS.c Creators: Tang, Yong Collection: Cells |
Views: 9/10
|
| Abstract |
|
Mitochondria–nucleus (mitonuclear) retrograde signaling via nuclear import of otherwise mitochondrial targeted factors occurs during mitochondrial unfolded protein response (UPRmt), a mechanism that counters mitochondrial and cellular stresses. Other than nuclear encoded proteins, mitochondrial DNA (mtDNA)-encoded peptides, such as humanin, are known to have important pro-survival and metabolic regulatory functions. A recent report has indicated that another mtDNA-encoded peptide, the mitochondrial open reading frame of the 12S rRNA-c (MOTS-c), could translocate into the nucleus upon stress induction. In the nucleus, MOTS-c binds to DNA and regulates the transcription of stress response genes in concert with other transcription factors. This is the first clear example of a mitochondria-derived peptide (MDP) acting in the nucleus to affect transcriptional responses to stress. Thus, MOTS-c may bear some characteristics of a ‘mitokine’ factor that mediates mitohormesis, influencing cell survival as well as organismal health and longevity.
Added by: Dr. Enrique Feoli Last edited by: Dr. Enrique Feoli |
| Notes |
|
A mitochondrial stress signal, or a ‘mitokine’, could confer protection and promote survival, while priming the cell’s readiness for subsequent insults with increasing severity. Ristow has previously coined the term ‘mitohormesis’ for such a phenomenon [9]. Apparently, the range of action for this elusive mitokine is not limited within a cell, and at least in C. elegans, it has been shown that mitochondrial stress in one tissue type confers protection in other tissues [5]. In fact, a very recent report from Dillin’s laboratory has shown that retromer-dependent Wnt signaling is critical for this propagation of mitochondrial stress signals from the nervous system to peripheral tissues [13]. Wnt may thus be a prime candidate for a mitokine. The mitohormetic signal(s) are known to affect cellular and organismal aging pathways, which involve key factors that impinge on cell/tissue survival and metabolic health, such as the mechanistic target of rapamycin (mTOR) [56] and the nicotinamide adenine dinucleotide (NAD+)-SIRT1 pathways [10]. Activation of these pathways results in transcriptomic and epigenetic changes in the genome that promotes health and life span extension in model organisms [54,55]. MOTS-c also appears to bear some characteristics of a mitokine molecule. In this regard, it is worth noting that a MOTS-c m.1382A>C polymorphism, which is specific for the Northeast Asian population, may speculatively underlie the longer life span of the Japanese [38]. MOTS-c and other MDPs would no doubt be subjects of further investigation along this line of translational interest.
Added by: Dr. Enrique Feoli Last edited by: Dr. Enrique Feoli |