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Published on: November 18, 2022
Mitochondrial-encoded MOTS-c prevents pancreatic islet destruction in autoimmune diabetes
Byung Soo Kong1, Se Hee Min1, Changhan Lee2
1Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea.
Abstract:
Mitochondria are principal metabolic organelles that are increasingly unveiled as immune regulators. However, it is currently not known whether mitochondrial-encoded peptides modulate T cells to induce changes in phenotype and function. In this study, we found that MOTS-c (mitochondrial open reading frame of the 12S rRNA type-c) prevented autoimmune β cell destruction by targeting T cells in non-obese diabetic (NOD) mice. MOTS-c ameliorated the development of hyperglycemia and reduced islet-infiltrating immune cells. Furthermore, adoptive transfer of T cells from MOTS-c-treated NOD mice significantly decreased the incidence of diabetes in NOD-severe combined immunodeficiency (SCID) mice. Metabolic and genomic analyses revealed that MOTS-c modulated T cell phenotype and function by regulating T cell receptor (TCR)/mTOR complex 1 (mTORC1) signaling. Type 1 diabetes (T1D) patients had a lower serum MOTS-c level than did healthy controls. Furthermore, MOTS-c reduced T cell activation by alleviating T cells from the glycolytic stress in T1D patients, suggesting therapeutic potential. Our findings indicate that MOTS-c regulates the T cell phenotype and suppresses autoimmune diabetes.
Insights
Mitochondrial peptide MOTS-c (mitochondrial open reading frame of the 12S rRNA type-c) prevents autoimmune diabetes by regulating T cells. Lower MOTS-c levels in type 1 diabetes patients suggest its therapeutic potential.
Area of Science:
- Immunology
- Metabolic research
- Mitochondrial biology
Background:
- Mitochondria are key metabolic organelles involved in immune regulation.
- The role of mitochondrial-encoded peptides in modulating T cell function remains largely unknown.
Purpose of the Study:
- To investigate if mitochondrial peptide MOTS-c influences T cell phenotype and function.
- To determine MOTS-c's potential in preventing autoimmune diabetes.
Main Methods:
- Studied MOTS-c effects in non-obese diabetic (NOD) mice.
- Utilized adoptive T cell transfer experiments.
- Performed metabolic and genomic analyses to understand signaling pathways.
- Measured serum MOTS-c levels in type 1 diabetes (T1D) patients.
Main Results:
- MOTS-c prevented autoimmune beta cell destruction and ameliorated hyperglycemia in NOD mice.
- MOTS-c modulated T cell phenotype and function by regulating T cell receptor (TCR)/mTOR complex 1 (mTORC1) signaling.
- Adoptive transfer of T cells from MOTS-c-treated mice reduced diabetes incidence.
- Lower serum MOTS-c levels were observed in T1D patients compared to healthy controls.
- MOTS-c alleviated T cell glycolytic stress, reducing T cell activation in T1D patients.
Conclusions:
- MOTS-c regulates T cell phenotype and function, suppressing autoimmune diabetes.
- MOTS-c demonstrates therapeutic potential for type 1 diabetes.
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