Humanin peptide suppresses apoptosis by interfering with Bax activation

Bin Guo, Dayong Zhai, Edelmira Cabezas, Kate Welsh, Shahrzad Nouraini, Arnold C. Satterthwait and John C. Reed ()
Additional contact information
Bin Guo: The Burnham Institute
Dayong Zhai: The Burnham Institute
Edelmira Cabezas: The Burnham Institute
Kate Welsh: The Burnham Institute
Shahrzad Nouraini: The Burnham Institute
Arnold C. Satterthwait: The Burnham Institute
John C. Reed: The Burnham Institute

Nature, 2003, vol. 423, issue 6938, 456-461

Abstract: Abstract Bax (Bcl2-associated X protein) is an apoptosis-inducing protein that participates in cell death during normal development and in various diseases1. Bax resides in an inactive state in the cytosol of many cells. In response to death stimuli, Bax protein undergoes conformational changes that expose membrane-targeting domains, resulting in its translocation to mitochondrial membranes, where Bax inserts and causes release of cytochrome c and other apoptogenic proteins2. It is unknown what controls conversion of Bax from the inactive to active conformation. Here we show that Bax interacts with humanin (HN), an anti-apoptotic peptide of 24 amino acids encoded in mammalian genomes3,4. HN prevents the translocation of Bax from cytosol to mitochondria. Conversely, reducing HN expression by small interfering RNAs sensitizes cells to Bax and increases Bax translocation to membranes. HN peptides also block Bax association with isolated mitochondria, and suppress cytochrome c release in vitro. Notably, the mitochondrial genome contains an identical open reading frame, and the mitochondrial version of HN can also bind and suppress Bax. We speculate therefore that HN arose from mitochondria and transferred to the nuclear genome, providing a mechanism for protecting these organelles from Bax.

Date: 2003
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/nature01627 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:423:y:2003:i:6938:d:10.1038_nature01627

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature01627

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().