2. Academic Validation
  3. Mitochondrial-derived peptides: Antidiabetic functions and evolutionary perspectives

Mitochondrial-derived peptides: Antidiabetic functions and evolutionary perspectives

  • Peptides. 2024 Feb:172:171147. doi: 10.1016/j.peptides.2023.171147.
Satadeepa Kal 1,  Sumana Mahata 2,  Suborno Jati 3,  Sushil K Mahata 4
Affiliations

Affiliations

  • 1 Department of Medicine, University of California San Diego, La Jolla, CA, USA.
  • 2 Department of Anesthesiology, Riverside University Health System, Moreno Valley, CA, USA.
  • 3 Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA, USA.
  • 4 Department of Medicine, University of California San Diego, La Jolla, CA, USA; VA San Diego Healthcare System, San Diego, CA, USA. Electronic address: smahata@health.ucsd.edu.
PMID: 38160808 DOI: 10.1016/j.peptides.2023.171147
Abstract

Mitochondrial-derived Peptides (MDPs) are a novel class of bioactive microproteins encoded by short open-reading frames (sORF) in mitochondrial DNA (mtDNA). Currently, three types of MDPs have been identified: Humanin (HN), MOTS-c (Mitochondrial ORF within Twelve S rRNA type-c), and SHLP1-6 (small Humanin-like peptide, 1 to 6). The 12 S ribosomal RNA (MT-RNR1) gene harbors the sequence for MOTS-c, whereas HN and SHLP1-6 are encoded by the 16 S ribosomal RNA (MT-RNR2) gene. Special genetic codes are used in mtDNA as compared to nuclear DNA: (i) ATA and ATT are used as start codons in addition to the standard start codon ATG; (ii) AGA and AGG are used as stop codons instead of coding for arginine; (iii) the standard stop codon UGA is used to code for tryptophan. While HN, SHLP6, and MOTS-c are encoded by the H (heavy owing to high guanine + thymine base composition)-strand of the mtDNA, SHLP1-5 are encoded by the L (light owing to less guanine + thymine base composition)-strand. MDPs attenuate disease pathology including Type 1 diabetes (T1D), Type 2 diabetes (T2D), gestational diabetes, Alzheimer's disease (AD), cardiovascular diseases, prostate Cancer, and macular degeneration. The current review will focus on the MDP regulation of T2D, T1D, and gestational diabetes along with an emphasis on the evolutionary pressures for conservation of the amino acid sequences of MDPs.

Keywords

Diabetes; Humanin; MOTS-c; Mitochondrial peptides; and small humanin-like peptides.

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