Journal September 16, 2026 5 min read

MOTS-c: reported timelines in the literature

MOTS-c is a mitochondrial-derived peptide studied for its roles in metabolism, inflammation, and cellular stress responses. This page summarizes reported timelines and findings from preclinical and clinical research, wit

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What is MOTS-c?

MOTS-c (mitochondrial open reading frame of the 12S rRNA type-c) is a mitochondrial-derived peptide (MDP) encoded within the 12S rRNA gene of mitochondrial DNA [1][11]. It is also referred to as a mitochondrial-encoded host defense peptide (HDP) and a mitokine [1][11]. The peptide sequence is Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg, with a molecular weight of approximately 2.2 kDa [4]. MOTS-c is amphipathic and cationic, consistent with the chemistry of known HDPs [1].

The work on MOTS-c centres on its role as a mitochondrial-derived regulator of metabolic and inflammatory pathways, with reported interactions involving the NLRP3 inflammasome, Nrf2 signalling, and LAT1-mediated cellular uptake [2][4].

Research Studies

MOTS-c and antibacterial host defense

MOTS-c was identified as a mitochondrial-encoded host defense peptide with direct antibacterial and immunomodulatory functions [1]. In laboratory studies, MOTS-c targeted Escherichia coli and other pathogens, and its peptide chemistry was consistent with known HDPs [1]. This work was conducted in vitro and in animal models; human data are not reported in this source.

MOTS-c and inflammasome activation in diabetic rats

In a high-fat diet and streptozotocin-induced type 2 diabetes mellitus (T2DM) rat model, MOTS-c treatment significantly reduced fasting blood glucose and circulating C-reactive protein levels, while selectively modulating plasma inflammatory markers [2]. The study investigated NLRP3 inflammasome activity in systemic and cardiac tissues [2]. These findings are animal-only; no human dosing or outcomes are reported.

MOTS-c and Hashimoto's thyroiditis

A cross-sectional study compared circulating MOTS-c levels in patients with Hashimoto's thyroiditis (HT; n=90) and age- and sex-matched healthy controls [3]. The study reported reduced circulating MOTS-c levels in HT patients, reflecting integrated autoimmune and metabolic dysregulation [3]. This is an observational human study; it does not establish causality or treatment effects.

R13A-MOTS-c and radiation-induced lung injury

An engineered variant, R13A-MOTS-c, was created by substituting the polar arginine at position 13 with alanine, increasing the hydrophobicity index from -0.938 to -0.544 and improving cellular uptake [4]. In models of radiation-induced lung injury, R13A-MOTS-c attenuated injury via Nrf2 activation and mitochondrial protection, with uptake mediated by LAT1 [4]. This work was conducted in vitro and in animal models; human data are not reported.

MOTS-c and atrial fibrillation

In an AngII-induced mouse model and primary cardiac cells, MOTS-c attenuated atrial fibrillation by suppressing fibrosis and mitochondrial dysfunction [5]. Human atrial tissues were also analysed, showing expression of MOTS-c [5]. The therapeutic potential was evaluated in animal and cell models; human plasma levels were measured but no human intervention data are reported.

MOTS-c and myocardial ischemia-reperfusion injury

A cross-sectional study of 72 acute myocardial infarction (AMI) patients undergoing percutaneous coronary intervention (PCI) examined the association between serum MOTS-c levels and myocardial ischemia-reperfusion injury (MIRI) [6]. Patients were divided into MIRI (n=34) and non-MIRI (n=38) groups, and MOTS-c levels were measured in peripheral serum and intracoronary blood [6]. This is an observational human study; it does not establish causality or treatment effects.

MOTS-c and polycystic ovary syndrome

A study investigated differences in MOTS-c levels between adolescents with polycystic ovary syndrome (PCOS) and those without, as well as associations with metabolic parameters and the m.1382A>C polymorphism [7]. The m.1382A>C polymorphism has been linked to increased risk of type 2 diabetes in men [7]. This is an observational human study; it does not establish causality or treatment effects.

MOTS-c and renal transplantation

A prospective controlled study (NCT07678073) aims to compare the effects of sevoflurane general anesthesia and combined spinal-epidural anesthesia on ferroptosis, humanin, and MOTS-c levels in renal transplantation [8]. The study is designed to investigate ischemia-reperfusion injury and graft function [8]. This is an ongoing clinical study; results are not yet reported.

MOTS-c in sepsis-induced cardiomyopathy

A review reports that MOTS-c is a mitochondrial-derived peptide implicated in sepsis-induced cardiomyopathy (SICM), a condition characterized by inflammatory dysregulation, mitochondrial dysfunction, and metabolic disturbance [9]. The review discusses mechanisms and translational potential [9]. This is a review article; it does not present new experimental data.

MOTS-c and mesenchymal stromal cells

A study reports that MOTS-c activates metabolic signalling but blunts reparative function in human mesenchymal stromal cells (MSCs) [10]. The work notes that obesity compromises MSC metabolism and reparative capacity, and that MOTS-c regulates cellular metabolism [10]. This is an in vitro study using human cells; no animal or human in vivo data are reported.

MOTS-c and inflammatory lung diseases

A review reports that MOTS-c is a mitochondrial-derived microprotein (mitokine) encoded within the 12S rRNA gene that exerts intracrine, paracrine, and endocrine effects across multiple tissues [11]. It notes that MOTS-c modulates oxidative stress and may become a potential treatment for inflammatory lung diseases [11]. This is a review article; it does not present new experimental data.

MOTS-c and cardiac ischemia-reperfusion injury

A study reports that MOTS-c preserves mitochondrial subpopulation bioenergetics and genome integrity to attenuate cardiac ischemia-reperfusion injury [12]. The work notes that mitochondrial dysfunction contributes to myocardial ischemia-reperfusion injury through impaired bioenergetics, oxidative stress, and disruption of mitochondrial homeostasis [12]. This is a preclinical study; human data are not reported.

Reported timelines in the literature

The table below summarizes the reported timelines and model systems for key studies on MOTS-c. Timelines refer to the duration of observation or treatment in each study, as reported in the evidence.

Study	Model	Reported timeline
Antibacterial host defense [1]	In vitro, animal	Not specified
Inflammasome activation in T2DM [2]	Rat model	Not specified
Hashimoto's thyroiditis [3]	Human cross-sectional	Not specified
Radiation-induced lung injury [4]	In vitro, animal	Not specified
Atrial fibrillation [5]	Mouse model, primary cells	Not specified
Myocardial ischemia-reperfusion injury [6]	Human cross-sectional	Not specified
Polycystic ovary syndrome [7]	Human observational	Not specified
Renal transplantation [8]	Human prospective	Ongoing

Note: The evidence block does not provide specific timelines (e.g., hours, days, weeks) for most studies. Where timelines are not specified, this table reflects that absence.

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