MOTS-c restores mitochondrial respiration in T2D heart
Various · Frontiers in Physiology · 2025 · Preclinical
In a type-2-diabetes rat model, MOTS-c improved cardiac mitochondrial respiration and delayed weight gain.
Mitochondrial-derived peptide
A mitochondrial-derived "mitokine" studied as an exercise-mimetic and metabolic regulator.
At a glance
Overview
A 16-mer encoded within mitochondrial DNA, discovered in 2015.
Studied for insulin sensitivity, metabolic flexibility and exercise adaptation. A Phase 2a prediabetes trial marks its move toward human outcomes.
Mechanism
Activates AMPK and, under metabolic stress, translocates to the nucleus to regulate stress-adaptation genes.
Research
Various · Frontiers in Physiology · 2025 · Preclinical
In a type-2-diabetes rat model, MOTS-c improved cardiac mitochondrial respiration and delayed weight gain.
Atakan MM, et al. · The Journal of Physiology · 2024 · Review
Reviews mitochondrial-derived peptides and MOTS-c's role in metabolism and the exercise response.
PMID 38170165 · Preclinical · 2024 · Preclinical
MOTS-c attenuated immobilisation-induced muscle atrophy by suppressing lipid infiltration.
Trial registry · Clinical trial registry · 2026 · Clinical trial registry
The first controlled human outcome study; defines what should be measured and separates mechanism from hype.
Lee C, et al. · Cell Metabolism · 2015 · Foundational
The original discovery paper describing MOTS-c and its AMPK-linked metabolic effects.
Evidence summary
Built on robust, consistent preclinical evidence for metabolic and exercise-related benefits, with its first controlled human trial now underway - one of the most exciting frontiers in mitochondrial and longevity research.