MOTS-c is one of the most searched mitochondrial-derived peptides, and almost every search hides the same question: what is the MOTS-c dose, and what protocol did the studies use? The honest answer is more nuanced than most pages admit. MOTS-c has been characterised in cell cultures and rodent experiments, but there is no established, validated human dosing protocol. This article lays out what the peer-reviewed research actually did, the administration routes, regimens and dose ranges reported in animal studies, and why those numbers cannot be read as a human instruction. For the full mechanistic reference, see our MOTS-c monograph; the research-grade material itself is our MOTS-c lyophilised peptide.
What MOTS-c actually is
MOTS-c (mitochondrial ORF of the 12S rRNA type-c) is a small peptide of 16 amino acids (sequence MRWQEMGYIFYPRKLR, molecular weight ~2.2 kDa) encoded not in the nucleus but inside the 12S ribosomal RNA region of mitochondrial DNA. That makes it a mitochondrial-derived peptide (MDP), part of a class of signalling molecules that includes humanin and the SHLP family [1][5].
Mechanistically, MOTS-c acts largely through AMP-activated protein kinase (AMPK), the cell's master fuel-sensing switch. It interferes with the folate cycle and one-carbon metabolism, which drives accumulation of AICAR, an endogenous AMPK activator, and shifts cells from anabolic toward catabolic programs: more glucose uptake, more fatty-acid oxidation, more mitochondrial biogenesis [1]. Under metabolic stress such as fasting, glucose restriction or oxidative stress, MOTS-c translocates from the cytoplasm to the nucleus in an AMPK-dependent manner, where it engages antioxidant-response (NRF2/ARE) gene programs [2]. This dual cytoplasmic-and-nuclear behaviour is the mechanistic core that any dosing discussion has to sit on top of.
MOTS-c was first identified computationally, by scanning the mitochondrial genome for short open reading frames hidden inside the 12S rRNA gene, and then confirmed as a real, translated peptide. That a molecule encoded deep inside the mitochondrion can leave it, act on cytoplasmic signalling and even enter the nucleus is what made MDPs a distinct research field rather than a footnote to mitochondrial biology [1][5].
Why there is no established human MOTS-c dose
This is the part most "protocol" pages skip. As of writing there are no interventional human clinical trials of MOTS-c, no published Phase 1 dose-finding study, no approved indication, no validated human dose. What exists in humans is observational: MOTS-c circulates measurably in plasma, its levels are modulated by physical exercise, and people with type 2 diabetes tend to show lower mitochondrial-derived-peptide levels than controls [3][5]. Human genetics adds one more thread, a MOTS-c coding polymorphism (K228Q) was associated with longevity in a Japanese male cohort [4]. These are association and mechanism studies, not dosing trials. None of them tell you a milligram figure for a person.
Because of that, everything below describes what researchers dosed in animals. It is reference information about published experiments, not a recommendation, and not something to convert into a human regimen.
Dose data: why it lives in the reference
The MOTS-c doses in the literature were reported in animal models as milligrams per kilogram of body weight, not as a human dose. We deliberately keep those numbers out of the article as instruction: the study data and the caveats around it are collected in the reference MOTS-c: dosing schedule.
Why a mouse mg/kg is not a human dose
The single most common mistake is to take a mouse figure like "5 mg/kg" and multiply it by a person's body weight. That is pharmacologically wrong. Standard allometric scaling (the FDA (U.S. Food and Drug Administration) human-equivalent-dose approach) accounts for the fact that smaller animals have faster metabolism per kilogram: a mouse dose is divided by roughly 12 to estimate a human-equivalent mg/kg, and even that conversion is only a starting point for a first-in-human safety study, not a therapeutic dose. On top of that, MOTS-c has a very short circulating half-life, on the order of minutes, because plasma and tissue proteases degrade it rapidly [5], so route, frequency and formulation matter as much as the raw number. None of this has been worked out for humans, which is exactly why a validated human protocol does not exist.
Route, form and reconstitution in research
Research MOTS-c ships as a lyophilised (freeze-dried) powder for stability, and is brought into solution before use, in laboratory work, typically with bacteriostatic or sterile water. The concentration you get depends on the vial size and the volume of solvent added; our peptide reconstitution calculator shows the arithmetic (mg per vial ÷ mL of solvent = mg/mL), which is the same math whatever the peptide. In the animal studies above the solution was injected IP or SC; because the peptide is cleared quickly, the published protocols relied on repeated dosing rather than a single administration [3][5][6].
Our MOTS-c is supplied as a lyophilised powder, HPLC (high-performance liquid chromatography, a purity-testing method)-verified to ≥98–99% purity, in 10 mg and 40 mg vials, each batch documented with a lot-specific certificate of analysis. It is laboratory material only.
Storage and handling
Lyophilised peptide is the stable form, kept dry, cold and out of light it tolerates storage and shipping well. Once reconstituted, a peptide solution is far more fragile: it should be kept refrigerated, protected from repeated freeze-thaw cycles and from heat and light, and treated as a short-shelf-life preparation. These are general peptide-handling practices; they are about material integrity in a research setting, not administration guidance.
Research use only
This article is compiled from publicly available, peer-reviewed sources and is provided for reference and informational purposes only. It is not medical advice and not a recommendation for use. MOTS-c is an experimental compound and is not an approved drug. Any products mentioned are supplied strictly for laboratory research use, they are not intended for human or animal consumption, nor for diagnostic or therapeutic use. Every dose and result described above was obtained in controlled experimental conditions and must not be interpreted as an instruction or protocol for people.
The full list of sources with links, is in the monograph: MOTS-c.
