MOTS-c

MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA-c) is a 16-amino-acid peptide encoded within a small open reading frame inside the mitochondrial 12S ribosomal RNA gene. It was first identified and characterized by Lee et al. in Cell Metabolism (2015) as a mitochondrial-derived peptide (MDP) with bioactivity outside the mitochondrion. Our research-grade MOTS-c is for in vitro research only.

The MOTS-c sequence is MRWQEMGYIFYPRKLR (Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg), 16 amino acids long, with an approximate monoisotopic molecular weight of ~2174 Da. The sequence is encoded within the 12S rRNA region of mitochondrial DNA in a non-canonical open reading frame.

Lee et al. (2015) reported that MOTS-c targets the folate cycle, inhibiting methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) and de novo purine biosynthesis. The resulting accumulation of AICAR (the ribotide ZMP) is an endogenous AMPK activator that phosphorylates AMPKα at Thr172, linking mitochondrial peptide signaling to cytosolic energy sensing.

Yes - Kim et al. (2018, Cell Metabolism) reported that under metabolic stress (glucose restriction, oxidative challenge), MOTS-c translocates from mitochondria to the nucleus, where it regulates adaptive nuclear gene expression including antioxidant response element (ARE) and NFE2L2/Nrf2-dependent stress response genes. This represents a mitochondrial-to-nucleus retrograde signaling mode.

Reynolds et al. (2021, Nature Communications) reported that MOTS-c administration in aged mice improved physical performance and skeletal muscle function in preclinical models of age-related decline. Circulating MOTS-c levels have also been reported to decrease with age in human cohorts (Cobb et al. 2016), positioning MOTS-c as a research probe for mitochondrial-derived aging biology.

Lyophilized MOTS-c should be stored at -20°C for long-term stability. Once reconstituted in bacteriostatic water, it should be refrigerated at 2-8°C and used within 14 days. Avoid repeated freeze-thaw cycles and protect from light. For research use only - not for human consumption.