Mitochondrial-derived peptide · Also known as Mitochondrial ORF of the 12S rRNA Type-C
A 16-amino-acid peptide encoded by the mitochondrial genome that acts as a key regulator of metabolic homeostasis. Animal studies show it prevents obesity, improves insulin sensitivity, and enhances exercise capacity, but no human clinical trials have been completed.
MOTS-c was discovered in 2015 by researchers at the University of Southern California and represents a new class of signaling molecules. mitochondrial-derived peptides. It is naturally produced and found in blood plasma, but levels decline with age. In preclinical studies, MOTS-c prevented diet-induced obesity, reversed insulin resistance, and improved exercise performance in aged mice. It is currently listed as a prohibited substance by WADA due to its performance-enhancing potential. Clinical development has been slow due to challenges with reliable delivery systems.
MOTS-c primarily works by activating AMPK (AMP-activated protein kinase), the master switch for cellular energy regulation. It does this by inhibiting the folate-methionine cycle, which leads to accumulation of AICAR, an endogenous AMPK activator. Activated AMPK shifts cells into energy-efficient mode. enhancing glucose uptake, promoting fatty acid oxidation, improving mitochondrial respiration, and suppressing fat storage and gluconeogenesis.
Under metabolic stress conditions, MOTS-c translocates from mitochondria to the cell nucleus, where it directly regulates gene expression related to metabolic homeostasis and antioxidant defense. This nuclear signaling role makes it unique among metabolic peptides. MOTS-c also improves skeletal muscle glucose metabolism and activates brown adipose tissue, contributing to its anti-obesity effects observed in animal models.
200-500 mcg/day or 5 mg 2-3x/week
First 2-4 weeks5-10 mg/week (split into 2-3 doses)
8-12 week cyclesMost side effects tend to improve as your body adjusts.