What is MOTS-c?

From the PeptideWhiz library entry. "As described" sections summarize claims made in the sources; they are not PeptideWhiz endorsements.

What it is

A 16-amino-acid peptide encoded in mitochondrial DNA. Released under metabolic stress and after eating. Called an "exercise mimetic," and a retrograde signal from mitochondria to the nucleus.

Mechanism (as described)

• Glucose and insulin: activates AMPK; GLUT4 moves to the membrane and glucose enters muscle (insulin-independent); insulin sensitivity improves.
• Mitochondria: raises PGC-1α/NRF1/TFAM (biogenesis) and SIRT1/SIRT3; boosts mitophagy (clears broken mitochondria).
• Fuel switch: moves cells from glucose to fatty-acid oxidation; discussed for fatty liver; reduces ROS.
• Inflammation: shuts down NLRP3, lowers TNF-α/IL-6, eases age-related inflammation.
• Brain: crosses the blood-brain barrier, raises BDNF, supports neurogenesis and brain insulin sensitivity, steadies the circadian clock and sleep.
• Heart: better cardiac metabolism after infarction.

Additional points (as described)

• Overload vs. adaptation: building mitochondria needs amino acids, magnesium, iron, zinc, NAD+ and CoQ10. Heavy fatigue, fog or weakness means too much too fast or missing cofactors.
• Some people get welts or itchy red spots at the start, so ease in and dilute well.
• Pairs with TB-500 after heart damage; supports fatty-liver support (FGF21).
• More isn't better: many people are described as doing better with fewer compounds rather than more.

FDA Compounding Panel (July 2026)

At its July 23-24, 2026 meeting, the FDA Pharmacy Compounding Advisory Committee recommended adding MOTS-c (free base and acetate) to the Section 503A bulks list, for the uses FDA reviewed (obesity and osteoporosis). FDA's own briefing documents had proposed not adding it.

• The vote is advisory and non-binding. It is not FDA approval, and it does not by itself allow pharmacies to compound MOTS-c. FDA would have to finish rulemaking to change the final list (21 CFR 216.23), which included no peptides as of October 2026.
• Reported tally (yes-no-abstain): 7-5-2, as reported in law-firm meeting reports. FDA had not posted official minutes or vote results when checked on October 19, 2026.
• FDA: July 23-24, 2026 PCAC meeting materials (substances under consideration)
• FDA: July 23-24, 2026 PCAC final agenda
• eCFR: 21 CFR 216.23, the final 503A bulks list