Comparison

Humanin vs MOTS-c

Function

While Humanin exerts neuroprotective and cytoprotective effects in models of Alzheimer’s disease, ischemia, and metabolic stress, reducing apoptosis and improving cell survival7136141, MOTS-c improves insulin sensitivity, enhances glycolysis, reduces oxidative stress, and shows protective effects in models of metabolic syndrome, aging, and ischemia-reperfusion injury8135146.

Mechanism

While Humanin works as a mitochondrial-derived 24-amino-acid peptide that protects cells against diverse apoptotic insults by interacting with cell-surface cytokine receptor complexes and intracellular targets, thereby activating pro-survival STAT3 and other pathways7136141, MOTS-c is a 16-amino-acid mitochondrial-derived peptide that translocates to the nucleus under metabolic stress and regulates glucose and lipid metabolism largely via activation of AMPK and modulation of mTOR and folate-cycle–linked pathways854140146.

Length and Sequence

Humanin is 24 amino acids long, whereas MOTS-c is shorter as it has a length of 16 amino acids. Humanin is made up of a sequence of Methionine, Alanine, Proline, Arginine, Glycine, Phenylalanine, Serine, Cysteine, Leucine, Leucine, Leucine, Leucine, Leucine, Threonine, Serine, Glutamic acid, Isoleucine, Aspartic acid, Leucine, Proline, Valine, Lysine, Arginine, Arginine, Alanine. MOTS-c is made up of a sequence of Methionine, Arginine, Tryptophan, Glutamine, Glutamic acid, Methionine, Glycine, Tyrosine, Isoleucine, Phenylalanine, Tyrosine, Proline, Arginine, Lysine, Leucine, Arginine.

Receptor

Humanin

Binds a trimeric cytokine receptor complex consisting of CNTFR, WSX-1, and gp130, and can also signal via the G-protein–coupled receptor FPRL1/FPR2136141

MOTS-c

No dedicated cell-surface receptor has been definitively identified; signaling is primarily described via intracellular AMPK and related metabolic pathways8135146

Organism or Origin

Humanin

Human mitochondrial peptide encoded within the 16S rRNA gene region7685

MOTS-c

Human mitochondrial peptide encoded in the 12S rRNA gene region54146

Gene

Humanin

MT-RNR2

MOTS-c

MT-RNR1

Related articles

No related articles are linked to these peptides yet.

Sources

7Evidence of natural selection in the mitochondrial-derived peptides ..., https://www.nature.com/articles/s41598-023-41053-0
53Frequently Asked Questions, https://www.peptidejournal.org/peptides/humanin-mitochondrial-peptide-research
76Humanin - Wikipedia, https://en.wikipedia.org/wiki/Humanin
85MT-RNR2 - Wikipedia, https://en.wikipedia.org/wiki/MT-RNR2
141Humanin: a harbinger of mitochondrial-derived peptides? - PMC - NIH, https://pmc.ncbi.nlm.nih.gov/articles/PMC3641182/
8Mitochondrial-encoded peptide MOTS-c prevents pancreatic islet ..., https://www.nature.com/articles/s12276-025-01521-1
54MOTS-c - Wikipedia, https://en.wikipedia.org/wiki/MOTS-c
135MOTS-c Promotes Glycolysis via AMPK-HIF-1α-PFKFB3 ... - PubMed, https://pubmed.ncbi.nlm.nih.gov/40035775/
146MOTS-c: A promising mitochondrial-derived peptide for therapeutic ..., https://pmc.ncbi.nlm.nih.gov/articles/PMC9905433/