Mitochondria Are Signalling Organelles

2–25 min read

Mitochondria are usually introduced as the structures responsible for producing cellular energy. That description is correct, but increasingly incomplete.

Research has established mitochondria as signalling organelles capable of communicating information about metabolic stress to the rest of the cell. One particularly interesting development has been the identification of small peptides encoded within mitochondrial DNA.

MOTS-c is a 16-amino-acid mitochondrial-derived peptide encoded within the 12S rRNA region of the mitochondrial genome. Experimental work in animal models suggests that under metabolic stress, MOTS-c can translocate to the nucleus and influence expression of genes associated with metabolic adaptation.

This makes the molecule scientifically unusual: genetic information contained within the mitochondrion appears capable of generating a peptide that subsequently participates in communication with the nuclear genome.

Research has explored potential relationships between MOTS-c, metabolic homeostasis, exercise physiology and ageing, predominantly in cell and animal models. More recent experimental research has also investigated potential roles involving innate immunity and host defence, an area that remains at an early and unsettled stage.

Much of the therapeutic interest surrounding MOTS-c, however, remains ahead of the clinical evidence. Findings involving metabolic regulation, exercise capacity, ageing and immune function have predominantly emerged from cellular and animal models rather than controlled human research.

That distinction matters. The significance of mitochondrial-derived peptides may ultimately be broader than any individual compound. Their discovery challenges the older conception of mitochondria as passive cellular power plants and instead places them within a network of metabolic, nuclear and potentially immune communication -- a reframing of mechanism, not yet a demonstrated human benefit.

Research Status

Emerging and predominantly preclinical. The founding metabolic and nuclear-signalling findings are well replicated in cell and animal models; controlled human data are not yet established.

Selected Research

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, 2015.
DOI: 10.1016/j.cmet.2015.02.009 · PMID: 25738459
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, 2018.
DOI: 10.1016/j.cmet.2018.06.008 · PMID: 29983246
Zheng Y, Wei Z, Wang T. MOTS-c: A Promising Mitochondrial-Derived Peptide for Therapeutic Exploitation. Frontiers in Endocrinology, 2023.
DOI: 10.3389/fendo.2023.1120533 · PMID: 36761202

Related Research