Pro-apoptotic members of the Bcl-2 protein family play a pivotal role in the initiation of apoptosis as factors causing mitochondrial outer membrane permeabilization (MOMP). Of recent interest are endogenous ligands that inhibit their MOMP activity. Mitochondrial-derived peptides (MDP) are a recently identified class of mitochondrial retrograde signaling molecules and have been observed regulating age-related disease progression. One of the MDPs, humanin (HN), has been reported to have specific interactions with some of the Bcl-2 proteins as well as being a potent apoptosis inhibitor. HN somehow interferes with the oligomerization of Bax and Bid, preventing their interaction and associated MOMP-inducing membrane localization. We describe the fibrillation of HN triggered by the addition of Bax or Bid. They form an amyloid-like structure verified by Thioflavin T binding and electron microscopy that can be altered by biologically relevant HN mutations. Furthermore, the Bcl-2 proteins are physically incorporated into the fibers, which protect them from proteolysis. Our finding reveals for the first time a novel mechanism for Bcl-2 inhibition by sequestration into stable fibril structures with HN. This newly discovered HN fibrillation could represent a new paradigm for efforts towards developing HN as a therapeutic that focalizes around the Bcl-2 family.

Bax induces amyloid-like fiber formation of humanin peptides

Macromolecular Chemistry: The Second Century

[Author Benefits](https://scimeetings.acs.org/?utm_source=pubs_content_marketing&utm_medium=website&utm_campaign=0320_MCF_NPI_Launch_Spring_Homepage&ref=pubs_content_marketing)

[How to use SciMeetings](https://storage.googleapis.com/dl.morressier.com/acs/SciMeetings-ACSSpring2020-HowToGuide_M3020-Final.pdf)

[Frequently Asked Questions](https://storage.googleapis.com/dl.morressier.com/acs/SciMtng_ACSNMSp2020_FAQ_M3120_Final.pdf)

ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.