A yeast BH3-only protein mediates the mitochondrial pathway of apoptosis Academic Article uri icon

Overview

MeSH Major

  • Apoptosis
  • Apoptosis Regulatory Proteins
  • Mitochondria
  • Peptide Fragments
  • Proto-Oncogene Proteins
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Signal Transduction

abstract

  • Mitochondrial outer membrane permeabilization is a watershed event in the process of apoptosis, which is tightly regulated by a series of pro- and anti-apoptotic proteins belonging to the BCL-2 family, each characteristically possessing a BCL-2 homology domain 3 (BH3). Here, we identify a yeast protein (Ybh3p) that interacts with BCL-X(L) and harbours a functional BH3 domain. Upon lethal insult, Ybh3p translocates to mitochondria and triggers BH3 domain-dependent apoptosis. Ybh3p induces cell death and disruption of the mitochondrial transmembrane potential via the mitochondrial phosphate carrier Mir1p. Deletion of Mir1p and depletion of its human orthologue (SLC25A3/PHC) abolish stress-induced mitochondrial targeting of Ybh3p in yeast and that of BAX in human cells, respectively. Yeast cells lacking YBH3 display prolonged chronological and replicative lifespans and resistance to apoptosis induction. Thus, the yeast genome encodes a functional BH3 domain that induces cell death through phylogenetically conserved mechanisms.

publication date

  • July 20, 2011

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3160254

Digital Object Identifier (DOI)

  • 10.1038/emboj.2011.197

PubMed ID

  • 21673659

Additional Document Info

start page

  • 2779

end page

  • 92

volume

  • 30

number

  • 14