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Medical Guide

Low MOTS-c in PCOS: What Does Mitochondrial Peptide Biology Tell Us?

In a Scientific Reports study, serum MOTS-c levels were found to be lower in 40 women with PCOS and 40 matched controls; a difference in the same direction was also observed in the muscle biopsy subgroup. We also evaluate the study's methodological correction dated September 9, 2026.

Scientific Trust Index
64/100
Moderate trust
Level of evidence: Cross-sectional human study; small muscle biopsy subgroup
What does this score mean?

The study includes 80 women matched for age and BMI, and the serum finding is supported by a muscle biopsy subgroup. However, a cross-sectional design cannot establish causality, the muscle subgroup consists of only 6+6 individuals, and a correction regarding the serum measurement method was published on September 9, 2026.

What did the study investigate?

It investigated whether MOTS-c, a mitochondrial-derived peptide, changes in the circulation and skeletal muscle of women with PCOS and its relationship with metabolic/hormonal characteristics.

How was it conducted?

Forty women diagnosed with PCOS according to the Rotterdam criteria were compared with 40 healthy controls matched for age and BMI. Serum MOTS-c was measured by ELISA. In the muscle biopsy subgroup, MOTS-c expression was evaluated by Western blot in vastus lateralis tissue in 6 PCOS and 6 controls.

What was found?

Serum MOTS-c was 220.2 ± 147.6 pg/mL in the PCOS group and 498.3 ± 224.4 pg/mL in controls (p<0.001). Muscle MOTS-c expression was found to be 74.2 ± 15.2 arbitrary units in the PCOS group and 100.0 ± 8.5 arbitrary units in the control group (p=0.005). Serum MOTS-c showed a weak inverse correlation with total testosterone and total cholesterol.

Limitations of the study

Due to the cross-sectional design, it cannot be said whether low MOTS-c is a cause or consequence of PCOS. The muscle biopsy sample size is very small. Diet and structured physical activity were not fully controlled. Additionally, on September 9, 2026, a correction was published updating the brand, sensitivity, and measurement range information of the serum MOTS-c ELISA kit.

What does it mean clinically?

The findings support that PCOS may be related to mitochondrial peptide biology and make MOTS-c interesting as a research biomarker. However, this study does not demonstrate that MOTS-c injection is effective or safe in the treatment of PCOS.

What do we not know yet?

The contribution of low MOTS-c to disease progression, whether it improves with lifestyle or standard PCOS treatments, and the benefit-risk balance of exogenous MOTS-c administration in humans remain unknown.

Reference

Kutuk IS, Akin S, Demirel H, et al. Reduced serum and skeletal muscle MOTS c levels in women with polycystic ovary syndrome are associated with mitochondrial dysfunction. Scientific Reports. 2026;16:8593. DOI: 10.1038/s41598-026-39687-x. Initial publication: February 12, 2026. Correction: September 9, 2026, DOI 10.1038/s41598-026-70401-z.

Related reading: MOTS-c: Mitochondrial Peptide and Metabolic Evidence · Peptide Applications and Level of Evidence

Written and medically reviewed by: Dr. Kerem Çağlayan · All Scientific Research

Detailed evaluation

Short answerIn women with PCOS, both circulating and skeletal muscle MOTS-c levels were found to be lower. This suggests that mitochondrial communication may play a role in the PCOS phenotype; it does not constitute evidence of treatment.

Why is the correction important?

The correction did not change the primary outcome numbers, but rather corrected the identity and analytical characteristics of the ELISA kit used for serum measurement. In terms of scientific transparency, it is important that this detail is explicitly stated on the page.

Conclusion

MOTS-c is a mitochondrial peptide worth investigating to understand the metabolic and hormonal phenotype in PCOS. Prospective and interventional human studies are required for clinical use.

Medical review note: This content has been prepared for the purpose of interpreting scientific data; it is not a personal diagnosis or treatment recommendation.

Medical editorial information

This content has been medically reviewed and approved by Dr. Kerem Çağlayan. It is intended for general education and does not replace an individual diagnosis or treatment plan.