ArticleActa pharmacologica Sinica2018
Humanin decreases mitochondrial membrane permeability by inhibiting the membrane association and oligomerization of Bax and Bid proteins.
Article in Acta pharmacologica Sinica, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 34 citations in OpenAlex.
- Mitochondria-derived peptides in liver disease: Emerging regulators of hepatic metabolism and therapeutic targets.Hepatology communications · 2026Review
- The intersection of mitochondria, lipids, and ferroptosis: a new avenue for dry age-related macular degeneration.Apoptosis : an international journal on programmed cell death · 2025Review
- Impact of Radiation Therapy on Serum Humanin and MOTS-c Levels in Patients with Lung or Breast Cancer.Current radiopharmaceuticals · 2024Observational
- Neuroprotective Action of Humanin and Humanin Analogues: Research Findings and Perspectives.Biology · 2023Review
- Review
- The neuroprotective effects of targeting key factors of neuronal cell death in neurodegenerative diseases: The role of ER stress, oxidative stress, and neuroinflammation.Frontiers in cellular neuroscience · 2023Review
- Recent developments of neuroprotective agents for degenerative retinal disorders.Neural regeneration research · 2022Review
- The Molecular Structure and Role of Humanin in Neural and Skeletal Diseases, and in Tissue Regeneration.Frontiers in cell and developmental biology · 2022Review
- Inducible fold-switching as a mechanism to fibrillate pro-apoptotic BCL-2 proteins.Biopolymers · 2021Article
- The Role of Mitochondria-Derived Peptides in Cardiovascular Diseases and Their Potential as Therapeutic Targets.International journal of molecular sciences · 2021Review
- Mitochondrial-derived peptides in aging and age-related diseases.GeroScience · 2021Review
- Novel Insights Into the Role of Mitochondria-Derived Peptides in Myocardial Infarction.Frontiers in physiology · 2021Review
- Protective Mechanism of Humanin Against Oxidative Stress in Aging-Related Cardiovascular Diseases.Frontiers in endocrinology · 2021Review
- Mitochondrial-Derived Peptides in Diabetes and Its Complications.Frontiers in endocrinology · 2021Review
- Humanin selectively prevents the activation of pro-apoptotic protein BID by sequestering it into fibers.The Journal of biological chemistry · 2020Article
- Review
- Testosterone increases apoptotic cell death and decreases mitophagy in Leber's hereditary optic neuropathy cells.Journal of applied genetics · 2020Article
- Humanin induces conformational changes in the apoptosis regulator BAX and sequesters it into fibers, preventing mitochondrial outer-membrane permeabilization.The Journal of biological chemistry · 2019Article
- Potential role of the cAMP/PKA/CREB signalling pathway in hypoxic preconditioning and effect on propofol‑induced neurotoxicity in the hippocampus of neonatal rats.Molecular medicine reports · 2019Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Humanin (HN) is a 24-residue peptide identified from the brain of a patient with Alzheimer's disease (AD). HN has been found to protect against neuronal insult caused by Aβ peptides or transfection of familial AD mutant genes. In order to elucidate the molecular mechanisms of HN neuroprotection, we explored the effects of HN on the association of Bax or Bid with lipid bilayers and their oligomerization in the membrane. By using single-molecule fluorescence and Förster resonance energy transfer techniques, we showed that Bax was mainly present as monomers, dimers and tetramers in lipid bilayers, while truncated Bid (tBid) enhanced the membrane association and tetramerization of Bax. HN (100 nmol/L) inhibited the self-association and tBid-activated association of Bax with the bilayers, and significantly decreased the proportion of Bax in tetramers. Furthermore, HN inhibited Bid translocation to lipid bilayers. HN could bind with Bax and Bid either in solution or in the membrane. However, HN could not pull the proteins out of the membrane. Based on these results, we propose that HN binds to Bax and cBid in solution and inhibits their translocation to the membrane. Meanwhile, HN interacts with the membrane-bound Bax and tBid, preventing the recruitment of cytosolic Bax and its oligomerization in the membrane. In this way, HN inhibits Bax pore formation in mitochondrial outer membrane and suppresses cytochrome c release and mitochondria-dependent apoptosis.
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Registered trials
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