What this means
Researchers studied how small changes to the humanin peptide affect its clumping with BID and BAX proteins. The work helps explain how humanin may influence cell death, but it does not show this happens in people.
Plain-English summary written by an AI model from the abstract. The original is below.
- Who it was tested in
- Cells in a lab and isolated mitochondria; no people or animals stated
- Kind of research
- A study
The science
- Original title
- Humanin variants differentially regulate BID fibrilization and suppress BAX- and BID-dependent membrane permeabilization.
- Authors
- Puja R, Morris DL, Wang ZH et al.
- Journal
- The Journal of biological chemistry
- Published
- Oct 23, 2026
- Study type
- Study
- PMID
- 42918500 ↗
Abstract
Humanin (HN), a mitochondria-derived peptide, exerts cytoprotective effects by modulating apoptosis through interactions with pro-apoptotic BCL-2 proteins, BAX and BID. Previous studies showed that HN induces β-sheet-rich fibrilization of BAX and truncated BID, suggesting a mechanism that may explain its cytoprotective function. Mutants of HN were shown to alter the morphology and fibrilization with BAX. In this study we tested whether the same HN variants can also influence fibrilization with BID, cleaved BID, or active truncated BID. We also evaluated the impact of fibrils formed between BAX or BID with HN on membrane morphology and permeability. The single Cysteine, C8, in HN is critical for fibrilization with all forms of BID. Whereas the central hydrophobic residues, L9 and L10, modulate fibril morphology with BID and cleaved BID; as they did with BAX. Interestingly, L12 has a differential effect on fibrilization with BID and BAX. Substitutions to the above residues of HN prevent formation of fibrils with truncated Bid. The HN fibril promotes vesicles to assemble as shown by electron microscopy, and this is moderated in the presence of BAX or BID. Vesicle leakage assays further demonstrated that HN reduced BAX- and tBID-mediated membrane permeabilization. Importantly, inhibition was strongly dependent on the order of sample addition. Finally, HN fibrils densely packed on isolated mitochondria in an organized parallel configuration. These findings extend the model of HN action by integrating BID activation-state specificity, HN residue-level determinants, and direct membrane association into a unified framework for HN-mediated regulation of mitochondrial apoptosis.
Puja R, Morris DL, Wang ZH et al. Humanin variants differentially regulate BID fibrilization and suppress BAX- and BID-dependent membrane permeabilization. The Journal of biological chemistry. 2026. doi:10.1016/j.jbc.2026.113675. PMID: 42918500. https://pubmed.ncbi.nlm.nih.gov/42918500/
Related research
Humanin treatment eased heart damage in diabetic mice
Mice with diabetes that got daily humanin for 15 days had less stress, inflammation, and cell death in the heart. This was tested in mice only, so it does not show the same would happen in people.
Humanin protein family may help steer cell stress responses
Researchers mapped how Humanin-related proteins connect to other proteins in a computer network. They suggest these proteins may guide stress responses, not just act alone. This is a model, so it does not show these proteins work this way in people.
Humanin, a small mitochondrial peptide, protected ovary cells from oxidative damage in lab tests
Researchers found that humanin helped human ovary cells and rat ovary tissue survive damage from oxidative stress. This was tested in cells and tissue, not people, so it does not show effects in humans.
AGEs-RAGE Axis and Mitochondrial-Derived Peptides in Advanced Chronic Kidney Disease: Interconnected Pathways Beyond Inflammation and Nutrition.
Background. Chronic kidney disease [CKD] is characterized by increased glycoxidative stress, inflammation, and mitochondrial dysfunction.
A humanin analog eased kidney damage in diabetic mice and cells
Researchers found a treated protein reduced kidney damage and cell death in diabetic mice. This work was in mice and cells, so it does not show the same effect in people.
Emerging regulators of human physiology and disease; sORF-encoded microproteins.
The human genome contains hundreds of thousands of short open reading frames (sORFs), yet their translational products, hereafter referred to as sORF-encoded microproteins (also historically termed micropeptides), have…