MOTS‐c: A Mitochondrial‐Encoded Regulator of the Nucleus

Abstract

Mitochondria are increasingly being recognized as information hubs that sense cellular changes and transmit messages to other cellular components, such as the nucleus, the endoplasmic reticulum (ER), the Golgi apparatus, and lysosomes. Nonetheless, the interaction between mitochondria and the nucleus is of special interest because they both host part of the cellular genome. Thus, the communication between genome‐bearing organelles would likely include gene expression regulation. Multiple nuclear‐encoded proteins have been known to regulate mitochondrial gene expression. On the contrary, no mitochondrial‐encoded factors are known to actively regulate nuclear gene expression. MOTS‐c (mitochondrial open reading frame of the 12S ribosomal RNA type‐c) is a recently identified peptide encoded within the mitochondrial 12S ribosomal RNA gene that has metabolic functions. Notably, MOTS‐c can translocate to the nucleus upon metabolic stress (e.g., glucose restriction and oxidative stress) and directly regulate adaptive nuclear gene expression to promote cellular homeostasis. It is hypothesized that cellular fitness requires the coevolved mitonuclear genomes to coordinate adaptive responses using gene‐encoded factors that cross‐regulate the opposite genome. This suggests that cellular gene expression requires the bipartite split genomes to operate as a unified system, rather than the nucleus being the sole master regulator.

PGC‐1α protects from myocardial ischaemia‐reperfusion injury by regulating mitonuclear communication

“…Therefore, it is conceivable that this cooperation resulted in genes which are adapted to environmental challenges via nuclear‐mitochondrial genetic interactions. Among the 1200 proteins in mitochondria, 13 are encoded by mitochondrial genes (mtDNA), 37 which account for a majority of the mitochondrial electron transfer chain complex 38 . As only a small fraction of mitochondrial proteins is encoded by mtDNA genes, the nucleus and mitochondria must continuously coordinate the transcription and translation of mitochondrial proteins, as well as translocations and imports.…”

Transposable elements, circular RNAs and mitochondrial transcription in age-related genomic regulation

“…mitochondrial rRNA sequences that encode MDPs. Nevertheless, by treating cells or animals with these peptides or by overexpressing them using genetic constructs, they have been shown to affect a number of age-related phenotypes (reviewed by Benayoun and Lee, 2019) and may play important roles during physiological aging (Table 3).…”

Extension of Mitogenome Enrichment Based on Single Long-Range PCR: mtDNAs and Putative Mitochondrial-Derived Peptides of Five Rodent Hibernators

“…These options and their combination could have implication for predicting the amino acid sequences of gau and other MDPsan issue that might be addressed in future experiments. Likewise, the highly conserved predictions of SHLP4 and 6 as well as of a four amino acid-core in MOTS-c ( (Lee et al, 2015); this study), a highly regulative peptide encoded by MT-RNR1 (Fuku et al, 2015;Lee et al, 2015Lee et al, , 2016Kim et al, 2018;Benayoun and Lee, 2019;Lu et al, 2019), argue for research beyond the classical model species of human and mice. For humanin our extended range of target species confirmed the mosaic of absent and putatively functional sORFs reported earlier (Logan, 2017).…”