The Mitochondrial-Derived Peptides, HumaninS14G and Small Humanin-like Peptide 2, Exhibit Chaperone-like Activity.

Okada AK, Teranishi K, Lobo F, Isas JM, Xiao J, Yen K, Cohen P, Langen R

Scientific reports10 Aug 2017Cited by 49 (Europe PMC)

PMID28798389PMCIDPMC5552803DOI10.1038/s41598-017-08372-5PepBankPUB-28798389

Summary

Mitochondrial-derived peptides (MDPs) and their analogs have emerged as wide-spectrum, stress response factors protective in amyloid disease models. MDP cytoprotective functions are generally attributed to anti-apoptotic activity, however, little is known about their capacity to facilitate the cell's unfolded protein response via direct interactions with amyloidogenic proteins. Here, we explored the effects of the MDP-analog, humaninS14G (HNG), and the MDP, small humanin-like peptide 2 (SHLP2), on the misfolding of islet amyloid polypeptide (IAPP), a critical pathogenic step in type 2 diabetes mellitus (T2DM). Our thioflavin T fluorescence studies show that HNG inhibits IAPP misfolding at highly substoichiometric concentrations. Seeded fluorescence and co-sedimentation studies demonstrate MDPs block amyloid seeding and directly bind misfolded, seeding-capable IAPP species. Furthermore, our electron paramagnetic resonance spectroscopy and circular dichroism data indicate MDPs do not act by binding IAPP monomers. Taken together our results reveal a novel chaperone-like activity wherein these MDPs specifically target misfolded amyloid seeds to inhibit IAPP misfolding which, along with direct anti-apoptotic activity and beneficial metabolic effects, make HNG and SHLP2 exciting prospects as T2DM therapeutics. These data also suggest that other mitochondrial stress response factors within the MDP family may be amenable to development into therapeutics for protein-misfolding diseases.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study4

1 result from studies that gave the peptide. No result from this study comes from people.

01LabIn vitro (cell-free)Activity measurement
In cell-free assays, humaninS14G (HNG) inhibited islet amyloid polypeptide misfolding at highly substoichiometric concentrations.
In plain wordsIn lab tests without cells, HNG blocked the misfolding of islet amyloid polypeptide at very low amounts.
Peptide
Humanin
Outcome
DecreaseIAPP misfolding (thioflavin T fluorescence)
Study
n: not reported in source
cell-free islet amyloid polypeptide (IAPP) misfolding assays
Outcome group
Receptor activity and mechanism · Pharmacology
Studied dose
Dose not stated
Source sentences
Summary
Our thioflavin T fluorescence studies show that HNG inhibits IAPP misfolding at highly substoichiometric concentrations.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we explored the effects of the MDP-analog, humaninS14G (HNG), and the MDP, small humanin-like peptide 2 (SHLP2), on the misfolding of islet amyloid polypeptide (IAPP), a critical pathogenic step in type 2 diabetes mellitus (T2DM).
Show in the study text Report a problemFND-2879838901

Studies that did not test the peptide alone3

In this study, Humanin was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Humanin.

02LabNot a test of Humanin aloneIn vitro (cell-free)Activity measurement
In cell-free assays, the mitochondrial-derived peptides HNG and SHLP2 blocked amyloid seeding of islet amyloid polypeptide.
In plain wordsIn lab tests without cells, two mitochondrial peptides, HNG and SHLP2, blocked amyloid seeding.
Peptide
Humanin
Outcome
DecreaseIAPP amyloid seeding by HNG and SHLP2
Study
n: not reported in source
cell-free islet amyloid polypeptide (IAPP) misfolding assays
Outcome group
Receptor activity and mechanism · Pharmacology
Source sentences
Summary
Seeded fluorescence and co-sedimentation studies demonstrate MDPs block amyloid seeding and directly bind misfolded, seeding-capable IAPP species.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we explored the effects of the MDP-analog, humaninS14G (HNG), and the MDP, small humanin-like peptide 2 (SHLP2), on the misfolding of islet amyloid polypeptide (IAPP), a critical pathogenic step in type 2 diabetes mellitus (T2DM).
In this study, Humanin was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Humanin.
Show in the study text Report a problemFND-2879838902
03LabNot a test of Humanin aloneIn vitro (cell-free)Activity measurement
In cell-free assays, the mitochondrial-derived peptides HNG and SHLP2 directly bound misfolded, seeding-capable islet amyloid polypeptide species.
In plain wordsIn lab tests without cells, two mitochondrial peptides, HNG and SHLP2, bound misfolded amyloid species.
Peptide
Humanin
Outcome
Not applicableBinding to misfolded IAPP species by HNG and SHLP2
Study
n: not reported in source
cell-free islet amyloid polypeptide (IAPP) misfolding assays
Outcome group
Receptor activity and mechanism · Pharmacology
Source sentences
Summary
Seeded fluorescence and co-sedimentation studies demonstrate MDPs block amyloid seeding and directly bind misfolded, seeding-capable IAPP species.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we explored the effects of the MDP-analog, humaninS14G (HNG), and the MDP, small humanin-like peptide 2 (SHLP2), on the misfolding of islet amyloid polypeptide (IAPP), a critical pathogenic step in type 2 diabetes mellitus (T2DM).
In this study, Humanin was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Humanin.
Show in the study text Report a problemFND-2879838903
04LabNot a test of Humanin aloneIn vitro (cell-free)Activity measurement
In cell-free spectroscopy, the mitochondrial-derived peptides HNG and SHLP2 did not act by binding islet amyloid polypeptide monomers.
In plain wordsIn lab tests without cells, two mitochondrial peptides, HNG and SHLP2, did not work by binding single amyloid units.
Peptide
Humanin
Outcome
No significant changeBinding to IAPP monomers by HNG and SHLP2
Study
n: not reported in source
cell-free islet amyloid polypeptide (IAPP) misfolding assays
Outcome group
Receptor activity and mechanism · Pharmacology
Source sentences
Summary
Furthermore, our electron paramagnetic resonance spectroscopy and circular dichroism data indicate MDPs do not act by binding IAPP monomers.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we explored the effects of the MDP-analog, humaninS14G (HNG), and the MDP, small humanin-like peptide 2 (SHLP2), on the misfolding of islet amyloid polypeptide (IAPP), a critical pathogenic step in type 2 diabetes mellitus (T2DM).
In this study, Humanin was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Humanin.
Show in the study text Report a problemFND-2879838904

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
13 Oct 2026, 21:44 UTC
Study results updated
Version 1
13 Oct 2026, 16:31 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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