What Is MOTS-c? Mitochondrial-Derived Peptide Structure

Key takeaways

• MOTS-c (Mitochondrial Open reading frame of the Twelve S rRNA type-c) is a 16-amino-acid peptide with the sequence MRWQEMGYIFYPRKLR.
• It is a mitochondrial-derived peptide (MDP): its short open reading frame is located within the mitochondrial 12S rRNA gene (MT-RNR1), not in the nuclear genome.
• Its molecular formula is C101H152N28O22S2, with an average molecular weight of approximately 2,174.6 g/mol.
• It contains two cysteine/methionine-class sulfur-bearing residues and three aromatic residues, giving it measurable UV absorbance at 280 nm.
• It ships as a lyophilized powder, is reconstituted in the lab with bacteriostatic or sterile water, and is stored frozen as a dry powder.
• Every Ascend Bio Labs batch carries a unique batch ID linking to a public third-party HPLC and LC-MS certificate of analysis.

MOTS-c is one of the more structurally distinctive compounds in the research-peptide catalog, not because of its length, but because of where its sequence comes from. Its name is an acronym: Mitochondrial Open reading frame of the Twelve S rRNA, type-c. Unlike most peptides studied in a lab, the short open reading frame that encodes MOTS-c sits inside the mitochondrial genome rather than the nuclear genome, which places it in a small family of so-called mitochondrial-derived peptides. This reference sticks to what the molecule physically is, its sequence, origin, molecular weight, form, reconstitution, and storage, and makes no statements about effects. It is a research-use-only material.

If you handle, characterize, or store MOTS-c on the bench, the practical questions are consistent: what is the exact 16-residue sequence, what molecular weight should a mass spectrum confirm, where does the sequence originate, and how should a lyophilized vial be reconstituted and kept stable? This post answers each in turn.

Peptide Class: A Mitochondrial-Derived Peptide

MOTS-c belongs to a class called mitochondrial-derived peptides (MDPs): short peptides whose coding sequences are embedded within mitochondrial ribosomal RNA genes rather than within nuclear protein-coding genes. This is structurally unusual. The vast majority of peptides described in research literature, and nearly every other compound in a peptide catalog, trace to nuclear-encoded precursors or are entirely synthetic designs. MOTS-c is encoded by a short open reading frame found within the mitochondrial 12S ribosomal RNA gene, designated MT-RNR1 in the human mitochondrial genome.

Because the sequence is naturally occurring rather than a designed analog, research-grade MOTS-c is reproduced by solid-phase peptide synthesis: the same chemistry used for shorter synthetic peptides, just extended across sixteen residues. For contrast on the short end of the spectrum, the four-residue chain covered in What Is Epithalon? is a useful reference point; at 16 residues MOTS-c is meaningfully longer and carries more analytical complexity through synthesis and purification.

The 16-Amino-Acid Sequence

MOTS-c is a 16-residue peptide. In standard single-letter notation, read from the N-terminus to the C-terminus, the sequence is MRWQEMGYIFYPRKLR. Spelled out residue by residue, that is methionine, arginine, tryptophan, glutamine, glutamic acid, methionine, glycine, tyrosine, isoleucine, phenylalanine, tyrosine, proline, arginine, lysine, leucine, arginine.

Two features of this sequence matter for lab characterization. First, it carries several basic residues, three arginines and one lysine, which give the unmodified peptide a net basic character at neutral pH and influence its behavior on reversed-phase and ion-exchange separations. Second, it contains three aromatic residues, one tryptophan and two tyrosines, so the peptide has genuine intrinsic UV absorbance at 280 nm, unlike short non-aromatic peptides that must be detected at lower wavelengths.

• Single-letter sequence (N to C): MRWQEMGYIFYPRKLR
• Length: 16 residues
• Basic residues: Arg x3, Lys x1 (net basic at neutral pH)
• Aromatic residues: Trp x1, Tyr x2 (UV absorbance at 280 nm)
• Sulfur-bearing residues: Met x2

Molecular Formula and Molecular Weight

The unmodified MOTS-c peptide has the molecular formula C101H152N28O22S2. Its average molecular weight is approximately 2,174.6 g/mol. The two sulfur atoms in the formula come from its two methionine residues. These values are what a laboratory should expect when confirming identity by mass spectrometry; an LC-MS run is generally used to verify that the observed mass matches this calculated value within instrument tolerance.

At roughly 2,175 Da, MOTS-c is a mid-sized peptide: larger than a tripeptide like the copper-binding compound in What Is GHK-Cu?, but well short of larger growth-hormone secretagogue chains. The presence of two methionines is worth flagging, because methionine side chains are oxidation-sensitive; an oxidized variant would register as a small mass shift on a mass spectrum and can show up as an additional peak on a purity chromatogram, which is exactly the kind of detail a careful COA review catches.

• Molecular formula: C101H152N28O22S2
• Average molecular weight: ~2,174.6 g/mol
• Sequence length: 16 residues
• Sulfur content: two methionine residues
• Net charge: basic at neutral pH

Origin Within the Mitochondrial 12S rRNA Gene

What makes MOTS-c structurally notable is the location of its coding sequence. It is encoded by a short open reading frame nested inside the mitochondrial 12S ribosomal RNA gene (MT-RNR1). In other words, a region of mitochondrial DNA that is primarily known for producing ribosomal RNA also harbors a short reading frame that maps to this 16-residue peptide. That dual use of the same genetic real estate is part of why mitochondrial-derived peptides were described relatively recently compared with classical nuclear-encoded peptides.

From a purely structural and analytical standpoint, the origin does not change how the compound is synthesized or tested in a research setting: a synthesized MRWQEMGYIFYPRKLR peptide is characterized by HPLC for purity and LC-MS for identity just like any other sequence. The mitochondrial origin is context for what the molecule is, not a claim about what it does.

Physical Form and Reconstitution

Research-grade MOTS-c is supplied as a lyophilized (freeze-dried) white-to-off-white powder in a sealed vial. Lyophilization removes water and yields a dry, stable form suited to cold storage and shipping. The vial is intended to be reconstituted into solution only at the point of use in the laboratory.

Reconstitution is typically performed by introducing a measured volume of bacteriostatic water or sterile water against the inside wall of the vial and allowing the powder to dissolve without vigorous agitation, which helps limit shear and foaming. The diluent and volume depend entirely on the concentration a given research protocol calls for. For broader handling context across compounds, see Peptide Storage and Cold-Chain Handling.

Nothing in this section is a use, dosing, or administration recommendation. Reconstitution here means preparing a solution for in-vitro laboratory work only.

Storage and Cold-Chain Handling

As a lyophilized powder, MOTS-c is best kept frozen and protected from light and moisture; many labs store dry peptide at -20 C or colder for long-term stability. Once reconstituted, the peptide solution is far less stable and should be refrigerated and used within a short window, with freeze-thaw cycling minimized because repeated cycles degrade peptides. The two oxidation-sensitive methionine residues are an additional reason to limit air exposure and prolonged time in solution at room temperature.

Cold-chain integrity from synthesis through shipping to the bench is part of why insulated, tracked shipping matters for these materials. The general principles, dry frozen storage, refrigerated working solution, minimal light and air exposure, and limited freeze-thaw, are covered in more depth in our Peptide Storage and Cold-Chain Handling reference. For a structural overview of a related research category, see GH Secretagogue Research Peptides.

Verifying Identity and Purity With a COA

For any research peptide, the certificate of analysis (COA) is the document that ties a physical vial to its analytical data. A meaningful COA reports the batch or lot identifier, the HPLC purity result, and the LC-MS identity confirmation, so the molecular weight observed on the mass spectrum can be checked against the ~2,174.6 Da expected for MOTS-c. Because the sequence carries two oxidation-prone methionines, a careful purity chromatogram is especially informative for this compound.

Ascend Bio Labs runs independent third-party HPLC for purity and LC-MS for molecular identity on every batch, and publishes a per-batch COA. Each vial carries a unique batch ID that links to its own certificate, and synthesis, testing, storage, and shipping are fully US-domestic with insulated, tracked delivery. The standard you should apply to any vendor is the same: a batch-specific COA you can actually inspect, with both purity and identity data attached to the exact lot you received.

Related research notes

• What Is Epithalon? Tetrapeptide Sequence and Molecular Weight
• GH Secretagogue Research Peptides: A Structural Overview
• Peptide Storage and Cold-Chain Handling: A Research Reference
• Semax vs Selank: Comparing Two Synthetic Peptide Structures