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A Review on Mitochondrial Derived Peptide Humanin and Small Humanin-Like Peptides and Their Therapeutic Strategies

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Abstract

The peptides are known to have diverse therapeutic indications and help cure many disease conditions. The mitochondrial genome comprises a novel class of micro peptides with various biological effects. Human mitochondrial peptides are among those that have a favourable impact on medicinal applications. Mitochondrial-derived peptides are small therapeutic peptides transcribed through mitochondrial DNA open-reading frames. Humanin is a mitochondrial peptide inhibiting complex I activity and reducing oxidative stress. It has significant apoptosis activity; therefore, it acts as an anti-apoptotic agent in the testis, boosting its reproductive role. It primarily affects cardioprotective and neuroprotective pathways, which operate as Alzheimer’s disease treatment agents. SHLPs and humanin were derived from mitochondrially encoded 16s rRNA small open reading frames. This peptide enhances mitochondrial functions and the survival of cells in response to oxidative stress. SHLP (1–6) has distinct and overlapping functions with humanin which regulate cell viability. The anti-diabetic activity is present in SHLP 2 and 3, which are insulin-resistant. Likewise, SHLP-6 has an apoptotic effect on cancer cells while it protects the cells against mitochondrial-mediated apoptosis. The mitochondrial-derived peptides increase insulin sensitivity, stimulating glucose absorption through peripheral tissues while decreasing glucose synthesis in the liver. These peptides are helpful in the treatment of multiple diseases. Thus, in this review discusses the mitochondrial peptide-humanin and SHLP types and their therapeutic potential.

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Abbreviations

SHLP:

Small humanin-like peptide

MDP:

Mitochondrial derived Peptide

HN:

Humanin

ATP:

Adenosine triphosphate

SmORF:

Small open reading Frame

ORF:

Open reading frame

DNA:

Deoxy-ribonucleic acid

rDNA:

Recombinant deoxy-ribonucleic acid

OXPHOS:

Oxidative phosphorylation system

mtDNA:

Mitochondrial deoxy-ribonucleic acid

rRNA:

Recombinant ribonucleic acid

HNG:

Humanin analogue

IncRNAs:

long non-coding RNAs

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Authors and Affiliations

  1. Institute of Biotechnology, Department of Medical Biotechnology and Integrative Physiology, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences, Thandalam, Chennai, Tamil Nadu, 602 105, India

    H. Thamarai Kannan, Praveen Kumar Issac & Nibedita Dey

  2. Department of Cariology, Saveetha Dental College and Hospitals, SIMATS, Chennai, Tamil Nadu, 600 077, India

    Ajay Guru

  3. Toxicology and Pharmacology Laboratory, Department of Biotechnology, Faculty of Science and Humanities, SRM Institute of Science and Technology, Kattankulathur, Chengalpattu District, Tamil Nadu, 603 203, India

    Jesu Arockiaraj

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All authors have agreed to be named as authors on this manuscript. Any work (data, text, or theories) of others besides the authors has been properly acknowledged. The work is original and not previously published. All data are true and accurate to the knowledge of the authors.

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Thamarai Kannan, H., Issac, P.K., Dey, N. et al. A Review on Mitochondrial Derived Peptide Humanin and Small Humanin-Like Peptides and Their Therapeutic Strategies. Int J Pept Res Ther 29, 86 (2023). https://doi.org/10.1007/s10989-023-10558-7

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