ArticleScientific reports2023
Evidence of natural selection in the mitochondrial-derived peptides humanin and SHLP6.
Article in Scientific reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 17 citations in OpenAlex.
- Mitokines as bioenergetic stress signals in cardiovascular disease: mitochondrial communication, endocrine adaptation, and translational implications.Journal of bioenergetics and biomembranes · 2026Review
- Climate-associated natural selection in the human mitochondrial genome.Molecular biology and evolution · 2026Article
- Small but mighty: mitochondrial DNA at the centre of retrograde signalling.Cell communication and signaling : CCS · 2026Review
- Mitochondrial-derived microproteins in lung disease: insights and implications.American journal of physiology. Lung cellular and molecular physiology · 2026Review
- Mitochondria-derived peptides in liver disease: Emerging regulators of hepatic metabolism and therapeutic targets.Hepatology communications · 2026Review
- Diagnostic relevance of Humanin, GAS5 and miR-21/miR-103 in prostate disease risk stratification.Clinical and experimental medicine · 2025Article
- Detecting mtDNA Effects with an Extended Pedigree Model: An Analysis of Statistical Power and Estimation Bias.Behavior genetics · 2025Article
- Noncoding RNA-encoded peptides in cancer: biological functions, posttranslational modifications and therapeutic potential.Journal of hematology & oncology · 2025Review
- Mitochondrial-derived microproteins: from discovery to function.Trends in genetics : TIG · 2025Review
- A Review on the Potential Role of Humanin Peptide and its Analogs in the Regulation of Autophagy Pathways for Therapeutic Application in Metabolic Disorders.Protein and peptide letters · 2025Review
- Review
- Mitochondrial-derived peptides: Antidiabetic functions and evolutionary perspectives.Peptides · 2024Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitochondrial-derived peptides are encoded by mitochondrial DNA but have biological activity outside mitochondria. Eight of these are encoded by sequences within the mitochondrial 12S and 16S ribosomal genes: humanin, MOTS-c, and the six SHLP peptides, SHLP1-SHLP6. These peptides have various effects in cell culture and animal models, affecting neuroprotection, insulin sensitivity, and apoptosis, and some are secreted, potentially having extracellular signaling roles. However, except for humanin, their importance in normal cell function is unknown. To gauge their importance, their coding sequences in vertebrates have been analyzed for synonymous codon bias. Because they lie in RNA genes, such bias should only occur if their amino acids have been conserved to maintain biological function. Humanin and SHLP6 show strong synonymous codon bias and sequence conservation. In contrast, SHLP1, SHLP2, SHLP3, and SHLP5 show no significant bias and are poorly conserved. MOTS-c and SHLP4 also lack significant bias, but contain highly conserved N-terminal regions, and their biological importance cannot be ruled out. An additional potential mitochondrial-derived peptide sequence was discovered preceding SHLP2, named SHLP2b, which also contains a highly conserved N-terminal region with synonymous codon bias.
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