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• W2775887773 endingPage "1021" @default.
• W2775887773 startingPage "1012" @default.
• W2775887773 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." @default.
• W2775887773 created "2018-01-05" @default.
• W2775887773 creator A5021118224 @default.
• W2775887773 creator A5083379478 @default.
• W2775887773 date "2017-12-21" @default.
• W2775887773 modified "2023-10-06" @default.
• W2775887773 title "Humanin decreases mitochondrial membrane permeability by inhibiting the membrane association and oligomerization of Bax and Bid proteins" @default.
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• W2775887773 doi "https://doi.org/10.1038/aps.2017.169" @default.
• W2775887773 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6256269" @default.
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• W2775887773 hasPublicationYear "2017" @default.
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