Bax function in the absence of mitochondria in the primitive protozoan Giardia lamblia.
Bax-induced permeabilization of the mitochondrial outer membrane and release of cytochrome c are key events in apoptosis. Although Bax can compromise mitochondria in primitive unicellular organisms that lack a classical apoptotic machinery, it is still unclear if Bax alone is sufficient for this, or whether additional mitochondrial components are required. The protozoan parasite Giardia lamblia is one of the earliest branching eukaryotes and harbors highly degenerated mitochondrial remnant organelles (mitosomes) that lack a genome. Here we tested whether human Bax expressed in Giardia can be used to ablate mitosomes. We demonstrate that these organelles are neither targeted, nor compromised, by Bax. However, specialized compartments of the regulated secretory pathway are completely ablated by Bax. As a consequence, maturing cyst wall proteins that are sorted into these organelles are released into the cytoplasm, causing a developmental arrest and cell death. Interestingly, this ectopic cargo release is dependent on the carboxy-terminal 22 amino acids of Bax, and can be prevented by the Bax-inhibiting peptide Ku70. A C-terminally truncated Bax variant still localizes to secretory organelles, but is unable to permeabilize these membranes, uncoupling membrane targeting and cargo release. Even though mitosomes are too diverged to be recognized by Bax, off-target membrane permeabilization appears to be conserved and leads to cell death completely independently of mitochondria.
Hehl
Adrian B
AB
Institute of Parasitology, University of Zürich, Zurich, Switzerland. Adrian.Hehl@access.uzh.ch
Regos
Attila
A
Schraner
Elisabeth
E
Schneider
André
A
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D016829:Giardia lamblia / Q000502:physiology*; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D008928:Mitochondria / Q000502:physiology; D011994:Recombinant Proteins / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000502:physiology*
D017931:DNA Primers; D011994:Recombinant Proteins; D051028:bcl-2-Associated X Protein