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Mitochondrial-derived peptides: Antidiabetic functions and evolutionary perspectives

Satadeepa Kal1, Sumana Mahata2, Suborno Jati3

  • 1Department of Medicine, University of California San Diego, La Jolla, CA, USA.

Peptides
|December 31, 2023
PubMed

Insights

Mitochondrial-derived peptides (MDPs) are novel microproteins from mitochondrial DNA that regulate diabetes. These peptides show conserved sequences, highlighting their evolutionary importance in metabolic health.

Area of Science:

  • Mitochondrial biology
  • Molecular genetics
  • Endocrinology

Background:

  • Mitochondrial-derived peptides (MDPs) are newly identified bioactive microproteins encoded by mitochondrial DNA (mtDNA).
  • Three main types exist: Humanin (HN), MOTS-c, and SHLP1-6, encoded by specific ribosomal RNA genes on mtDNA.
  • Mitochondrial genetic codes differ from nuclear DNA, utilizing unique start and stop codons and coding assignments.

Purpose of the Study:

  • To review the role of MDPs in regulating diabetes mellitus, including Type 1 (T1D), Type 2 (T2D), and gestational diabetes.
  • To explore the evolutionary conservation of MDP amino acid sequences.
  • To highlight MDPs' therapeutic potential in metabolic diseases.

Main Methods:

  • Review of existing literature on MDPs, mtDNA genetics, and diabetes.
  • Analysis of genetic codes and gene locations for MDPs within mtDNA.
  • Examination of studies investigating MDP function in diabetes models.

Main Results:

  • MDPs, including HN, MOTS-c, and SHLP peptides, are encoded on both heavy and light strands of mtDNA.
  • These peptides have demonstrated potential in attenuating pathologies associated with T1D, T2D, and gestational diabetes.
  • Amino acid sequences of MDPs exhibit significant evolutionary conservation.

Conclusions:

  • MDPs represent a critical link between mitochondrial function and metabolic regulation, particularly in diabetes.
  • The evolutionary conservation of MDPs underscores their fundamental biological roles.
  • Further research into MDPs could lead to novel therapeutic strategies for diabetes treatment.
Keywords:
DiabetesHumaninMOTS-cMitochondrial peptidesand small humanin-like peptides

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