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Study · In vitro (cell-free) · 2019

4 results

Humanin induces conformational changes in the apoptosis regulator BAX and sequesters it into fibers, preventing mitochondrial outer-membrane permeabilization.

Morris DL, Kastner DW, Johnson S, Strub MP, He Y, Bleck CKE, Lee DY, Tjandra N

The Journal of biological chemistry5 Nov 2019Cited by 30 (Europe PMC)

PMID31690630 (opens in a new tab)PMCIDPMC6916494 (opens in a new tab)DOI10.1074/jbc.ra119.011297 (opens in a new tab)PepBankPUB-31690630
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Summary

The mitochondrial, or intrinsic, apoptosis pathway is regulated mainly by members of the B-cell lymphoma 2 (BCL-2) protein family. BCL-2-associated X apoptosis regulator (BAX) plays a pivotal role in the initiation of mitochondria-mediated apoptosis as one of the factors causing mitochondrial outer-membrane permeabilization (MOMP). Of current interest are endogenous BAX ligands that inhibit its MOMP activity. Mitochondrial-derived peptides (MDPs) are a recently identified class of mitochondrial retrograde signaling molecules and are reported to be potent apoptosis inhibitors. Among them, humanin (HN) has been shown to suppress apoptosis by inhibiting BAX translocation to the mitochondrial outer membrane, but the molecular mechanism of this interaction is unknown. Here, using recombinant protein expression, along with light-scattering, CD, and fluorescence spectroscopy, we report that HN and BAX can form fibers together in vitro Results from negative stain EM experiments suggest that BAX undergoes secondary and tertiary structural rearrangements and incorporates into the fibers, and that its membrane-associating C-terminal helix is important for the fibrillation process. Additionally, HN mutations known to alter its anti-apoptotic activity affect fiber morphology. Our findings reveal for the first time a potential mechanism by which BAX can be sequestered by fibril formation, which can prevent it from initiating MOMP and committing the cell to apoptosis.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study4

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

  1. 01LabIn vitro (cell-free)Mechanism

    In vitro, humanin and BAX formed fibers together.

    In plain wordsIn lab tests, humanin and the BAX protein formed fibers together.

    Peptide
    Humanin
    Outcome
    Not applicableFiber formation by HN and BAX
    Study

    n: not reported in source

    Outcome group
    Receptor activity and mechanism · Cancer
    Studied dose
    Dose not stated

    Source sentences

    Summary
    using recombinant protein expression, along with light-scattering, CD, and fluorescence spectroscopy, we report that HN and BAX can form fibers together
  2. 02LabIn vitro (cell-free)Mechanism

    Negative stain EM suggested that BAX undergoes secondary and tertiary structural rearrangements and is incorporated into fibers with humanin.

    In plain wordsIn lab tests, electron microscopy suggested that BAX changes shape and joins the fibers formed with humanin.

    Peptide
    Humanin
    Outcome
    Not applicableBAX structural rearrangement and incorporation into fibers
    Study

    n: not reported in source

    Outcome group
    Receptor activity and mechanism · Cancer
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Results from negative stain EM experiments suggest that BAX undergoes secondary and tertiary structural rearrangements and incorporates into the fibers
  3. 03LabIn vitro (cell-free)Mechanism

    Negative stain EM suggested that the membrane-associating C-terminal helix of BAX is important for fibrillation with humanin.

    In plain wordsIn lab tests, the BAX tail region that attaches to membranes appeared to be needed for fiber formation with humanin.

    Peptide
    Humanin
    Outcome
    Not applicableRole of BAX C-terminal helix in fibrillation
    Study

    n: not reported in source

    Outcome group
    Receptor activity and mechanism · Cancer
    Studied dose
    Dose not stated

    Source sentences

    Summary
    its membrane-associating C-terminal helix is important for the fibrillation process.

Studies that did not test the peptide alone1

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.

  1. 04LabNot a test of Humanin aloneIn vitro (cell-free)Mechanism

    HN mutations known to alter its anti-apoptotic activity affected the morphology of HN-BAX fibers.

    In plain wordsIn lab tests, humanin mutations that change its anti-cell-death activity also changed the shape of the fibers.

    Peptide
    Humanin
    Outcome
    Not applicableFiber morphology with HN mutations
    Study

    n: not reported in source

    Outcome group
    Receptor activity and mechanism · Cancer

    Source sentences

    Summary
    Additionally, HN mutations known to alter its anti-apoptotic activity affect fiber morphology.

    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.

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.

  1. Version 2Current

    13 Oct 2026, 21:44 UTC

    Study results updated

  2. 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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