Peptide reference
MOTS-c
Mitochondrial ORF of the 12S rRNA-c ·Mitochondrial-derived peptide MOTS-c ·MOTSc
What cited sources report about MOTS-c
MOTS-c is a 16-amino-acid mitochondrial-derived peptide (MDP) encoded within a small open reading frame of mitochondrial DNA. The peptide is currently under review by the FDA Pharmacy Compounding Advisory Committee (PCAC), with a public meeting scheduled for July 23, 2026. As of the cited literature, MOTS-c has no FDA-approved indication and no marketing authorization in any major jurisdiction. The summaries below report what individual cited sources state; this page does not assert claims beyond what those sources report.
Behan et al. (2026) — American Journal of Physiology — Lung Cellular and Molecular Physiology
A 2026 review from the University of Pittsburgh Department of Medicine and the USC Leonard Davis School of Gerontology surveyed mitochondrial-derived microproteins (MDPs), including MOTS-c and Humanin. The authors observed that the published literature has predominantly focused on tissues with high mitochondrial density and on age-related diseases, and they outlined research gaps in pulmonary applications.
Most published work on MDPs has focused on MOTS-c and Humanin’s actions in tissues with high mitochondrial density (heart, skeletal muscle, and brain) or in disease states of advanced age—Alzheimer’s, cancer, and cardiovascular disease.
Hu et al. (2026) — Pathology — Research and Practice
A 2026 review synthesized the divergent signaling architectures of major mitochondrial-derived microproteins. The authors described MOTS-c as acting through an AMPK/NRF2-LARS1/mTORC1 pathway, and outlined translational considerations including MDP-targeted agonists, antagonists, and engineered delivery systems for neurodegenerative and oncologic indications.
This review synthesizes the divergent signaling architectures of major MDPs, including Humanin-FPR2/gp130, MOTS-c-AMPK/NRF2-LARS1/mTORC1, SHLP2-CXCR7, and SHMOOSE’s genotype-dependent activity, and outlines how these mechanisms produce disease-specific outcomes.
Fang et al. (2025) — Life Sciences
A review from the Auckland Bioengineering Institute catalogued associations between MOTS-c and type-2 diabetes mellitus risk factors and cardiac complications, and compiled exogenous MOTS-c dosing schedules used in preclinical metabolic-disease studies. The authors framed MOTS-c as a peptide whose insufficiency, in dysfunctional mitochondria, has been associated in published animal work with the pathological development of diabetes.
MOTS-c, a recently discovered mitochondria-derived peptide, plays a key role in regulating metabolic homeostasis and stress response.
PubChem — MOTS-c
The PubChem compound entry/search results for MOTS-c catalogue the peptide’s sequence and synonym set and link to underlying chemical and biological literature. The record disambiguates MOTS-c from other mitochondrial-derived microproteins such as Humanin and the SHLP family.
Coverage notes
Published MOTS-c literature is dominated by preclinical work in rodent metabolic-disease models and in cell-culture systems; the cited Auckland review (Fang 2025) explicitly compiled the heterogeneous preclinical dosing schedules that have been used. No completed Phase II/III clinical efficacy trials of exogenous MOTS-c are indexed on ClinicalTrials.gov as of the last_updated date — although MOTS-c appears in some trials as an observational biomarker (e.g., NCT04013568, NCT07438002). No FDA-approved indication exists. This page will be updated when the July 2026 PCAC briefing materials are released.