Comparison

Humanin vs SS-31

Function

While Humanin exerts neuroprotective and cytoprotective effects in models of Alzheimer’s disease, ischemia, and metabolic stress, reducing apoptosis and improving cell survival7136141, SS-31 improves mitochondrial bioenergetics, reduces oxidative stress, and shows protective effects in models of ischemia-reperfusion, neurodegeneration, and other mitochondrial disorders4637137.

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, SS-31 is a mitochondria-targeted tetrapeptide, d-Arg-dimethylTyr-Lys-Phe-NH2, that selectively binds cardiolipin in the inner mitochondrial membrane, stabilizing cristae structure, improving electron transport, and reducing ROS production4637137143.

Length and Sequence

Humanin is 24 amino acids long, whereas SS-31 is shorter as it has a length of 4 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. SS-31 is made up of a sequence of Arginine, dimethylTyr, Lysine, Phenylalanine.

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

SS-31

Cardiolipin-rich inner mitochondrial membrane; interacts with cardiolipin and associated mitochondrial proteins rather than a classical cell-surface receptor46137143

Organism or Origin

Humanin

Human mitochondrial peptide encoded within the 16S rRNA gene region7685

SS-31

Fully synthetic Szeto–Schiller tetrapeptide; not encoded in the genome4637

Gene

Humanin

MT-RNR2

SS-31

Not assigned in the current dataset.

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/
46Discovery of novel SS-31 (d-Arg-dimethylTyr-Lys-Phe-NH2 ... - PMC, https://pmc.ncbi.nlm.nih.gov/articles/PMC11409442/
56Discovery of novel SS-31 (d-Arg-dimethylTyr-Lys-Phe-NH2 ..., https://pubs.rsc.org/en/content/articlelanding/2024/ra/d4ra05517a
137Mitochondrial protein interaction landscape of SS-31 | PNAS, https://www.pnas.org/doi/10.1073/pnas.2002250117
143SS-31 Peptide: Mitochondrial Repair for Energy and Longevity, https://revolutionhealth.org/blogs/news/peptide-therapy-ss-31