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...

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Autores principales: Hehl, Adrian B., Regos, Attila, Schraner, Elisabeth, Schneider, André
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1871612/
https://www.ncbi.nlm.nih.gov/pubmed/17534438
http://dx.doi.org/10.1371/journal.pone.0000488
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author Hehl, Adrian B.
Regos, Attila
Schraner, Elisabeth
Schneider, André
author_facet Hehl, Adrian B.
Regos, Attila
Schraner, Elisabeth
Schneider, André
author_sort Hehl, Adrian B.
collection PubMed
description 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.
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spelling pubmed-18716122007-05-30 Bax Function in the Absence of Mitochondria in the Primitive Protozoan Giardia lamblia Hehl, Adrian B. Regos, Attila Schraner, Elisabeth Schneider, André PLoS One Research Article 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. Public Library of Science 2007-05-30 /pmc/articles/PMC1871612/ /pubmed/17534438 http://dx.doi.org/10.1371/journal.pone.0000488 Text en Hehl et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Hehl, Adrian B.
Regos, Attila
Schraner, Elisabeth
Schneider, André
Bax Function in the Absence of Mitochondria in the Primitive Protozoan Giardia lamblia
title Bax Function in the Absence of Mitochondria in the Primitive Protozoan Giardia lamblia
title_full Bax Function in the Absence of Mitochondria in the Primitive Protozoan Giardia lamblia
title_fullStr Bax Function in the Absence of Mitochondria in the Primitive Protozoan Giardia lamblia
title_full_unstemmed Bax Function in the Absence of Mitochondria in the Primitive Protozoan Giardia lamblia
title_short Bax Function in the Absence of Mitochondria in the Primitive Protozoan Giardia lamblia
title_sort bax function in the absence of mitochondria in the primitive protozoan giardia lamblia
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1871612/
https://www.ncbi.nlm.nih.gov/pubmed/17534438
http://dx.doi.org/10.1371/journal.pone.0000488
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