Mitochondrial-Encoded Peptide MOTS-c, Diabetes, and Aging-Related Diseases.

Diabetes & metabolism journal2023PMID: 36824008

View on PubMed DOI: 10.4093/dmj.2022.0333

Plain Language Summary

Review focusing on MOTS-c's role in diabetes—both T1DM and T2DM—and aging-related diseases, covering its regulation of glucose and lipid metabolism, insulin sensitivity, and its connections to cellular aging pathways including senescence and mitochondrial dysfunction, with discussion of its therapeutic potential as a diabetes and anti-aging intervention alongside other MDPs including humanin and SHLPs. Provides a diabetes-and-aging-focused MOTS-c reference. Synthesizes the mechanistic basis for MOTS-c as a dual-purpose therapeutic in diabetes and aging—establishing how a single mitochondrial genome-encoded peptide integrates insulin sensitivity, cellular survival, and aging pathway regulation to protect against multiple age-associated metabolic diseases simultaneously.

Abstract

Mitochondria are complex metabolic organelles with manifold pathophysiological implications in diabetes. Currently published mitochondrial-encoded peptides, which are expressed from the mitochondrial open reading frame of the 12S ribosomal RNA type-c (MOTS-c), 16S rRNA (humanin and short humanin like peptide 1-6 [SHLP1-6]), or small human mitochondrial open reading frame over serine tRNA (SHMOOSE) are associated with regulation of cellular metabolism and insulin action in age-related diseases, such as type 2 diabetes mellitus. This review focuses mainly on recent advances in MOTS-c research with regards to diabetes, including both type 1 and type 2. The emerging understanding of MOTS-c in diabetes may provide insight into the development of new therapies for diabetes and other age or senescence-related diseases.

Authors

Kong, Byung Soo; Lee, Changhan; Cho, Young Min

Keywords

AgingDiabetes mellitus, type 2Intracellular signaling peptides and proteinsMitochondria