A Mitochondrial Encoded Messenger at the Nucleus

Cheryl Qian Ying Yong; Bor Luen Tang

doi:10.3390/cells7080105

A Mitochondrial Encoded Messenger at the Nucleus

Cells. 2018 Aug 13;7(8):105. doi: 10.3390/cells7080105.

Authors

Cheryl Qian Ying Yong¹, Bor Luen Tang^{2

3}

Affiliations

¹ Department of Biochemistry, Yong Loo Lin School of Medicine, Singapore 117597, Singapore. a0127148@u.nus.edu.
² Department of Biochemistry, Yong Loo Lin School of Medicine, Singapore 117597, Singapore. bchtbl@nus.edu.sg.
³ NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore 117456, Singapore. bchtbl@nus.edu.sg.

Abstract

Mitochondria⁻nucleus (mitonuclear) retrograde signaling via nuclear import of otherwise mitochondrial targeted factors occurs during mitochondrial unfolded protein response (UPR^mt), 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.

Keywords: AMP-activated protein kinase (AMPK); humanin; mitochondria; mitochondrial open reading frame of the 12S rRNA-c (MOTS-c); mitochondrial unfolded protein response (UPRmt).