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Mitochondrial-derived peptides: MOTS-c, humanin and SHLPs

What mitochondrial-derived peptides are, how humanin, MOTS-c and the small humanin-like peptides were discovered, and where the research stands.

Peptides from the mitochondrial genome

Mitochondria carry their own small circle of DNA, separate from the DNA in the cell nucleus. For a long time it was thought to code only for a handful of proteins and RNAs used in energy production.

Since the early 2000s, researchers have found short open reading frames inside this mitochondrial DNA that code for small peptides. These are known as mitochondrial-derived peptides, or MDPs.

Humanin

Humanin was the first, described in 2001 by a Japanese research group. It is encoded within the region of mitochondrial DNA for the 16S ribosomal RNA, and has been studied mainly in cell and animal models of cell survival and stress.

MOTS-c

MOTS-c, a 16-amino-acid peptide, was described in 2015. It is encoded in the 12S ribosomal RNA region. Research has used cell and rodent models of metabolism, including glucose handling and responses to exercise.

Small humanin-like peptides (SHLPs)

A further group of six small humanin-like peptides, SHLP1 to SHLP6, was reported in 2016, also encoded in the 16S region. Less has been published on these than on humanin or MOTS-c.

Where the research stands

Work on mitochondrial-derived peptides is still at an early stage and mostly preclinical. None is an approved medicine.