Humanin

Humanin is a micropeptide encoded in the mitochondrial genome by the 16S ribosomal RNA gene, MT-RNR2. Its structure contains a three-turn α-helix, and no symmetry.

In in vitro and animal models, it appears to have cytoprotective effects.^[3][4][5][6]

Gene

Humanin is encoded in the mitochondrial genome by the 16S ribosomal RNA gene, MT-RNR2.^[7] Multiple paralogs are found in the nuclear genome (due to nuclear mitochondrial DNA segments) and are named MTRNR2L followed by a number. It is not entirely sure whether these paralogous isoforms are completely unexpressed.^[8]

Protein

The expressed peptide^[9] contains a three-turn α-helix, and has no symmetry.^[9]

The length of the peptide depends on where it is produced. If it is produced inside the mitochondria it will be 21 amino acids long.^[10] If it is produced outside the mitochondria, in the cytosol, it will be 24 amino acids long.^[10] Both peptides have been shown to have biological activity.^[10][11]

Other species

Humanin is the most well-

The mouse MT-RNR2 humanin ortholog is a pseudogene, so no humanin is produced from the mtDNA. However, the nuclear genome harbors (like in humans) many copies of mitochondrial genomes, and one copy of the humanin homolog, Gm20594 (J3QJY3), is actively expressed.^[13]

Function

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Humanin has several cytoprotective effects.^[14]

Interactions

Extracellular interaction with a tripartite receptor composed of

Intracellular interaction with BAX, tBID, IGFBP3, and TRIM11 may also be required for the effects of humanin.^{[11][17][18][19]}

Discovery

Humanin was the first mitochondria-derived peptide to be discovered.

Experiments using cultured cells have demonstrated that humanin has both neuroprotective as well as cytoprotective effects and experiments in rodents have found that it has protective effects in Alzheimer's disease models, Huntington's disease models and stroke models.[20]

Humanin is proposed to have myriad neuroprotective and cytoprotective effects. Both studies in cells and rodents have both found that administration of humanin or humanin derivatives increases survival and/or physiological parameters in

Beyond the possible neuroprotective effects, humanin protects against oxidative stress, atherosclerotic plaque formation, and heart attack.[26]^[27][28][29] Humanin activates chaperone-mediated autophagy in a dose-dependent manner.^[3] Humanin decreases production of inflammatory cytokines, which is part of its anti-apoptotic effect.^[4] Metabolic effects have also been demonstrated and humanin helps improve survival of pancreatic beta-cells, which may help with type 1 diabetes,^[30] and increases insulin sensitivity, which may help with type 2 diabetes.^[31][6] In rats, the humanin analog appears to normalize glucose levels and reduce diabetes symptoms.^[32]

Rattin shows the same ability as humanin to defend neurons from the toxicity of

Small humanin-like peptides are a group of peptides found in the mitochondrial 16S rRNA, and also possess retrograde signaling functions.

References