Limited · human
This cross-sectional study investigated circulating levels of MOTS-c — a mitochondria-derived peptide involved in metabolic and immune regulation — in patients with Hashimoto's thyroiditis (HT) compared to healthy controls. A total of 180 participants (90 HT patients and 90 age- and sex-matched healthy controls) were enrolled. The study found that circulating MOTS-c levels were significantly lower in HT patients than in controls. Lower MOTS-c levels were independently associated with insulin resistance and markers of autoimmune burden (such as thyroid autoantibodies). The authors propose that impaired mitochondrial signaling, as reflected by reduced MOTS-c, may contribute to the pathophysiology of thyroid autoimmunity and metabolic dysregulation seen in HT. The study's cross-sectional design limits causal inference — it is unclear whether reduced MOTS-c is a cause or consequence of HT. Additional limitations include the single-timepoint measurement, potential confounders not fully addressed, and the absence of longitudinal follow-up. The findings position MOTS-c as a candidate biomarker linking metabolic dysfunction and immune dysregulation in thyroid autoimmunity, though further prospective and mechanistic research is needed to confirm this relationship.
Journal of clinical medicine · May 2026DOI ↗ Limited · human
This observational cohort study measured serum levels of two circulating peptides — Nardilysin (NRDc) and MOTS-c — in 150 participants (118 kidney transplant recipients [KTRs] and 32 age-matched controls) to explore their potential roles as cardiometabolic biomarkers in this high-risk population. Using commercial ELISA kits, the researchers found that median serum NRDc and MOTS-c levels were significantly higher in KTRs compared to controls. Penalized logistic regression revealed an inverse association between elevated NRDc levels and prevalent cardiovascular (CV) disease in KTRs, suggesting that higher NRDc may be associated with lower odds of existing CV disease. KTRs were followed for a median of approximately 29 months, during which renal allograft loss and all-cause mortality were analyzed using Fine-Gray competing risk regression. The authors propose that elevated NRDc and MOTS-c in KTRs may reflect altered metabolic and inflammatory pathways unique to this population. Key limitations include the observational design, the relatively small and single-center cohort, the cross-sectional nature of the CV disease association, and the lack of incident CV event data. The authors acknowledge that longitudinal studies are needed to clarify causal relationships.
Kidney & blood pressure research · May 2026DOI ↗ Limited · human
This pilot observational study investigated the relationship between MOTS-c — a mitochondria-derived peptide — and cardiovascular risk markers in 32 stable peritoneal dialysis (PD) patients (mean age ~61 years, ~63% male). Researchers measured MOTS-c in three compartments: serum, urine, and peritoneal dialysate. Oxidative stress was assessed via plasma Advanced Oxidation Protein Products (AOPPs), and vascular stiffness was evaluated using carotid-femoral Pulse Wave Velocity (PWV), with echocardiography used to assess left ventricular systolic function. The study found that urinary MOTS-c was inversely correlated with AOPPs (suggesting a link to lower oxidative stress) and positively associated with PWV and left ventricular systolic function. Dialysate MOTS-c showed a strong inverse correlation with PWV and with both systolic and diastolic blood pressure, suggesting an association with a more favorable vascular profile. The authors propose a novel "Mitochondrial-Vascular Axis" in uremia and position MOTS-c as a potential biomarker. Key limitations include the very small sample size (n=32), pilot/cross-sectional design, single-center recruitment, and inability to establish causality from correlational data.
International urology and nephrology · May 2026DOI ↗ Limited · human
This study investigated the role of two mitochondrial-derived peptides (MDPs) — humanin (HN) and MOTS-c — in atrial fibrillation (AF), a common heart rhythm disorder. Researchers first examined human atrial tissue using public gene expression data, immunohistochemistry, and immunofluorescence, and measured plasma levels in a matched cohort of 39 AF patients and 39 sinus rhythm controls. They found that both peptides were significantly downregulated in AF tissue, with levels inversely correlated with fibrosis extent. Plasma MOTS-c was also reduced in AF patients and inversely correlated with NT-proBNP, a heart stress biomarker. Using an angiotensin II (AngII)-induced mouse AF model (n=36, male C57BL/6J), the study found that treatment with HNG (an HN analogue) or MOTS-c reduced AF inducibility and attenuated atrial fibrosis and hypertrophy. Peptide treatment was associated with improved mitochondrial structure, reduced fission proteins (Drp1, Fis1), and lower inflammatory cytokines. In vitro experiments in rat cardiomyocytes and fibroblasts showed reduced oxidative stress, fibroblast activation, proliferation, and migration. Exploratory RNA-sequencing suggested distinct mechanistic pathways. Key limitations include the small human cohort, the use of an animal model that may not fully replicate clinical AF, and the exploratory nature of mechanistic findings.
Biomedicines · May 2026DOI ↗ Limited · human
This cross-sectional study investigated the relationship between serum levels of MOTS-c — a mitochondria-derived peptide encoded in the 12S rRNA — and myocardial ischemia-reperfusion injury (MIRI) in patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI). Seventy-two AMI patients were divided into MIRI (n=34) and non-MIRI (n=38) groups. The study measured MOTS-c concentrations in both peripheral serum and intracoronary blood, alongside clinical variables. The MIRI group displayed lower systolic blood pressure, lower pre-operative TIMI grade, and lower HDL-C, while showing higher total ischemic time, door-to-balloon time, culprit vessel stenosis severity, Killip grade, and adverse event rates. Multivariate logistic regression identified postoperative peripheral serum MOTS-c as an independent protective factor against MIRI, and ROC analysis suggested potential predictive value for MIRI. Limitations include the small sample size, single-center cross-sectional design, lack of causal inference, and the absence of dynamic longitudinal monitoring of MOTS-c. The authors conclude that MOTS-c warrants further investigation as a novel biomarker and potential therapeutic target for MIRI, pending validation in larger prospective studies.
Biomedicines · Apr 2026DOI ↗ Limited · human
This observational case-control study investigated whether serum MOTS-c levels and the mitochondrial m.1382A>C gene polymorphism are associated with polycystic ovary syndrome (PCOS) in adolescents. A total of 246 participants aged 12–18 were enrolled: 121 diagnosed with PCOS (based on irregular menstrual cycles and clinical/biochemical hyperandrogenism) and 125 healthy controls with regular menstruation. Serum MOTS-c levels were measured by ELISA, and the m.1382A>C polymorphism was assessed by gene sequencing. The study found that mean serum MOTS-c levels were slightly higher in the PCOS group compared to controls, but this difference did not reach statistical significance (p = 0.059). No significant associations were observed between MOTS-c levels and anthropometric or metabolic parameters within the PCOS group. Notably, all participants carried the wild-type (A/A) genotype for the m.1382A>C polymorphism, making genetic association analysis impossible in this cohort. The authors concluded that MOTS-c may play only a minor role in PCOS pathophysiology. Limitations include the modest sample size, the adolescent-only population, the absence of polymorphism variability, and the cross-sectional design precluding causal inference.
Archives of endocrinology and metabolism · Apr 2026DOI ↗ Limited · human
This study investigated the role of MOTS-c, a mitochondrially encoded regulatory peptide, in protecting spermatogenesis. Researchers first measured serum MOTS-c levels in patients with oligoasthenozoospermia (a condition involving reduced and poorly motile sperm), finding these levels were significantly lower than in fertile controls and correlated positively with semen quality parameters. To model spermatogenic dysfunction mechanistically, the researchers used a microgravity-based mechanical stress model in mice, which induced decreased sperm concentration, disrupted seminiferous tubule architecture, and reduced spermatogonia counts. Exogenous MOTS-c administration was shown to ameliorate these impairments by suppressing oxidative stress and ferroptosis — a form of iron-dependent programmed cell death. The study identified SLC7A11 (Solute Carrier Family 7 Member 11), a known ferroptosis regulator, as a molecular target of MOTS-c. Loss- and gain-of-function experiments confirmed that SLC7A11 inhibits ferroptosis and oxidative stress while promoting spermatogonia proliferation. MOTS-c's protective effects were shown to depend, at least in part, on upregulating SLC7A11 under mechanical stress conditions. Limitations include the small and uncharacterized human cohort, reliance on an indirect mechanical stress model, and predominantly animal/cellular mechanistic data.
Free radical biology & medicine · Mar 2026DOI ↗ Limited · human
This observational study investigated circulating levels of MOTS-c — a mitochondrial-derived peptide involved in metabolic regulation — in adults with and without obesity, and examined whether levels changed after bariatric surgery. Researchers compared 22 lean controls with 32 obese participants scheduled for bariatric surgery, measuring MOTS-c concentrations alongside metabolic and inflammatory markers. A subset of 10 obese patients was followed longitudinally before and 6 months after surgery. Adipose tissue MOTS-c expression was also assessed via immunofluorescence in lean (n=6) and obese (n=14) subjects. The study found that circulating MOTS-c was significantly higher in obese versus lean individuals (273 vs. 223 pg/mL), and positively correlated with BMI and HOMA-IR. A notable biphasic relationship emerged between MOTS-c and HOMA-IR, with a sharp rise above a threshold of ~6.6 mmol/L×µU/mL. Despite significant weight and BMI reductions following bariatric surgery, MOTS-c levels did not change significantly post-operatively. Adipose tissue expression did not differ between groups. The authors suggest MOTS-c may reflect a compensatory metabolic response in obesity and insulin resistance. Key limitations include the small sample size, particularly in the longitudinal substudy, and the lack of an independent validation cohort.
Journal of clinical & translational endocrinology · Dec 2025DOI ↗