Fig 1. Schematic presentation of the mitochondrial genome encoding the MDPs in the 16S and 12S rRNAs.
Mitochondrial Derived Peptides (MDPs): Age-Dependent Regulators of Apoptosis, Insulin Sensitivity, and Inflammatory Markers
- Mitochondria are key players in aging and in the pathogenesis of age-related diseases. Recent mitochondrial transcriptome analyses revealed the existence of multiple small mRNAs with short open reading frames (sORFs) transcribed from mitochondrial DNA (mtDNA). These sORFS led to the discovery of MDPs encoded and transcribed by mitochondria.
- These newly discovered peptides are playing key roles in age-related diseases such as diabetes, Alzheimer's, cancer, atherosclerosis, etc.
- Under stress - stimulated by metabolic aging or disease mechanisms - MDPs are released from mitochondria into the cytosol. Furthermore, MDPs are released by retrograde signaling due to free radicals/reactive oxygen species (ROS) and calcium influx.
- Humanin (HN), a peptide encoded in the mtDNA 16S ribosomal RNA region, is a neuroprotective factor. An in silico search revealed additional peptides in the same region of mtDNA as humanin called small humanin-like peptides (SHLPs). The SHLPs differed in their ability to regulate cell viability in vitro. SHLP2 and SHLP3 significantly reduced apoptosis and the generation of reactive oxygen species, and improved mitochondrial metabolism in vitro.
- (Cobb L. J., et al., A 8 (4), 796-808 (2016); PMID: 27070352)
- MOTS-c (mitochondrial open reading frame of the 12S rRNAc) was found to reduce insulin resistance, to decrease obesity, and to promote homeostasis (Lee C., et al., Cell Met 21, 443-454 (2015)).