What Is MOTS-c?
MOTS-c, is a short name for the Mitochondrial Open Reading Frame of the 12S rRNA-c, which is a peptide encoded by the mitochondrial 12S rRNA gene [1, 2].
MOTS-c is composed of 16 amino acids and is highly expressed in response to stress or exercise [2]. It plays a crucial role in maintaining energy and stress homeostasis. It does so by acting mainly through the Folate-AICAR-AMPK pathway. As a result, it influences energy metabolism, insulin resistance, inflammatory response, exercise, aging and aging-related pathologies [1]. MOTS-c acts mainly through the Folate-AICAR-AMPK pathway [1].
MOTS-c can be found in various tissues and in plasma, but interestingly its levels decline with age [2]. Some research suggested that it has beneficial effects on age-related diseases including diabetes, cardiovascular diseases, osteoporosis, postmenopausal obesity and Alzheimer’s disease [2].
What Is MOTS-c Used For?
As suggested earlier, MOTS-c plays a crucial role in multiple processes within human health and disease. It is involved in the regulation of metabolic homeostasis, which refers to the balance of energy production and consumption in the body [1, 2]. That said, MOTS-c is not an approved drug or treatment for any disease.
In mice with lipopolysaccharide-induced acute lung injury, it has been found to attenuate body weight loss, pulmonary edema and inflammation [3]. Therefore it might be a potential candidate for treatment for this health condition.
In addition to this, it promotes muscle differentiation. It shows potential to be used in fighting against muscle wasting diseases, as it increases myotube formation in both murine models of muscle progenitor cells and humans as well [4].
In the context of metabolic diseases, MOTS-c has been found to improve insulin sensitivity and glucose metabolism. This indicates its potential benefits for metabolic conditions like obesity or diabetes [5, 6, 7]. With respect to bone metabolism, it promotes osteoblast proliferation, differentiation and mineralization as well as inhibiting osteoclast production [8]. In addition, the MOTS-c natural levels have been found to change in the blood of pregnant women with metabolic disorder, which further supports its potential role in maintaining metabolic balance during pregnancy.
In addition, it has also been associated with improved memory and cognitive function. It seems to enhance object and location recognition, memory formation and consolidation and ameliorate memory deficits induced by certain substances [9].
In terms of eyes, MOTS-c has been suggested to be a potential treatment for age-related retinal disorders like glaucoma, diabetic retinopathy or macular degeneration [10].
Lastly, MOTS-c levels have been found to change in the blood of pregnant women with metabolic disorders, suggesting a potential role in maintaining metabolic balance during pregnancy [11].
What Are The Side Effects Of MOTS-c?
Since MOTS-c peptide is not an approved drug for use, nor is it approved as a treatment for any disease, its side effects have not been explored properly in humans. However, in terms of safety, one study found that chronic administration of MOTS-c had little effect on liver, renal, lipid or cardiac function in mice [].
One study showed that the intraperitoneal administration (an injection to the body cavity) of MOTS-c, attenuated body weight loss and pulmonary edema and inhibited neutrophilic tissue infiltration in lung tissue [3]. Further, another study reported that MOTS-c treatment significantly enhanced AMPKα_{1/2} phosphorylation in the lumbar spinal cord of mice with neuropathic pain [13]. However, implications on the human body have not been explored. Further research is needed to fully understand the potential side effects of MOTS-c in humans.