MOTS-c

MOTS-c (mitochondrial open reading frame of the 12S rRNA type-c) is a mitochondrial-derived peptide composed of 16 amino acids encoded by the 12S rRNA region of the mitochondrial genome. ^{[1] [2]} It belongs to the class of mitochondrial-derived peptides, together with Humanin and the small humanin-like peptides (SHLPs). ^[3] Mitochondrial DNA was traditionally thought to encode only 37 genes, and the identification of mitochondrial-derived peptides such as MOTS-c expands that genetic repertoire. ^{[4] [5]} These peptides are viewed as active mitochondrial-encoded signals acting at the cellular and organismal level, a concept described as a mitochondrial hormone. ^[5] MOTS-c is being investigated as a potential exercise mimetic. ^[6]

Under metabolic stress, MOTS-c translocates to the nucleus, where it regulates a wide range of nuclear genes in response to metabolic dysfunction. ^{[2] [1]} In the nucleus it regulates the expression of stress adaptation-related genes carrying antioxidant response elements (ARE). ^[7] MOTS-c acts mainly through the folate-AICAR-AMPK pathway, thereby influencing energy metabolism, insulin resistance, inflammatory responses and aging-related pathologies. ^[7] Its main reported target is skeletal muscle, where it enhances glucose metabolism. ^{[5] [1]} Among mitochondrial-derived peptides

MOTS-c is colocalized to mitochondria in various tissues and is also found in plasma, so it can be studied as a circulating peptide. ^{[2] [1]} In humans, acute high-intensity exercise can increase MOTS-c concentrations in skeletal muscle and plasma. ^[10] Evidence that exercise training produces chronic changes in tissue or circulating levels is conflicting and may depend on the mode, duration and intensity of training and on participant characteristics. ^[10]

Plasma MOTS-c levels decline with age. ^{[2] [1]} Dynamic changes in MOTS-c expression have been closely linked to ageing and ageing-related diseases.