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MOTS-C vs SS-31

Two very different answers to the same research question: how to work at the mitochondrion.

Shared research areas:MetabolicCellular Longevity
ClassMitochondrial-derived peptide, 16 residuesMitochondria-targeting aromatic-cationic tetrapeptide (cardiolipin-binding)
Molecular weight2174.5 g/mol639.81 g/mol
CAS numberNot assigned / not specifiedNot assigned / not specified
Purity spec≥98%≥99%
Research areasMetabolic, Cellular LongevityCellular Longevity, Metabolic
Primary diluentSterile or bacteriostatic waterBacteriostatic water (0.9% benzyl alcohol)
Working windowCommonly worked with for 2–3 weeks at 2–8 °C.Commonly worked with for 3-4 weeks at 2-8 °C.
Lead degradation routeMethionine oxidation to the sulfoxide (+16 Da), and MOTS-c carries methionine at the N-terminus and internally.Adsorptive loss to plasticware from the cationic charge — the main practical concern.
Freeze–thawAliquot on reconstitution. Each vial opening introduces oxygen that acts on two susceptible residue types at once.Tolerant; the unnatural residues resist degradation. Aliquot as standard practice.
Light sensitivityProtect from light throughout — tryptophan photo-oxidation applies here as it does to DSIP.No specific light requirement beyond normal practice.

How they actually differ

MOTS-c is a signal that comes from the mitochondria — a peptide encoded in mitochondrial DNA, studied for the messages it sends out about metabolism. SS-31 (Elamipretide) goes the other way: it travels into the inner mitochondrial membrane and binds cardiolipin, studied for supporting the machinery in place. One is studied as an outgoing signal, the other as an on-site stabiliser. In handling, SS-31's strong positive charge calls for low-bind tubes, while MOTS-c carries a methionine and a tryptophan, so oxygen and light are its two vulnerabilities.

MOTS-C — origin

MOTS-c is encoded not in nuclear DNA but within the mitochondrial genome — specifically an open reading frame inside the 12S ribosomal RNA gene. Its discovery helped establish that mitochondria encode short signalling peptides that act on the rest of the cell, a genuinely recent addition to cell biology and the reason the compound attracted rapid research interest.

SS-31 — origin

SS-31 (Elamipretide) is a Szeto-Schiller aromatic-cationic tetrapeptide (D-Arg-2',6'-dimethyltyrosine-Lys-Phe-NH2) that concentrates in the inner mitochondrial membrane and binds cardiolipin, the lipid unique to that membrane. Its structure is the reason it is studied specifically at the mitochondrion rather than as a general antioxidant.

MOTS-C research themes

Mitochondrial-derived signalling

Part of a novel class demonstrating that mitochondria encode peptides acting systemically.

AMPK pathway

The most-studied signalling interaction, examined in metabolic and exercise models.

Insulin sensitivity

Investigated in glucose-metabolism research models.

Exercise and longevity biology

Studies have examined MOTS-c expression in relation to physical activity and ageing in animal models.

SS-31 research themes

Cardiolipin binding

Studied for selective association with cardiolipin in the inner mitochondrial membrane, the basis of its mitochondrial targeting.

Electron transport efficiency

Examined for effects on mitochondrial energy production in research models of mitochondrial dysfunction.

Oxidative stress

Investigated around reactive-oxygen-species handling at the mitochondrion.

MOTS-C handling

  • Use amber vials or wrap in foil; treat light protection as mandatory rather than precautionary.
  • Minimise vial openings — headspace oxygen is the practical driver of oxidation.
  • Use low-bind labware for dilute working solutions.

SS-31 handling

  • Reach room temperature before opening.
  • Use low-bind labware and buffers at low working concentrations to limit adsorption of the cationic peptide.
  • Aliquot and refrigerate.

Both third-party tested

Every Popular Peptides batch of MOTS-C and SS-31 is independently tested by HPLC and LC-MS with a published Certificate of Analysis. Enter a lot number to pull the COA for a specific vial.

MOTS-C reference

SS-31 reference

Related comparisons

MOTS-C and SS-31 are supplied strictly as research chemicals for in-vitro laboratory and research use only. They are not intended for human or animal consumption, diagnostic, or therapeutic use. This comparison summarizes published preclinical literature and laboratory handling data; it is not medical advice, not a claim of efficacy, and not usage guidance.