The mycotoxin phomoxanthone A disturbs the form and function of the inner mitochondrial membrane Article Swipe
Philip Böhler
,
Fabian Stuhldreier
,
Ruchika Anand
,
Arun Kumar Kondadi
,
David Schlütermann
,
Niklas Berleth
,
Jana Deitersen
,
Nora Hieke
,
Wenxian Wu
,
Marian Frank
,
Hendrik Niemann
,
Elisabeth Wesbuer
,
Andreas Barbian
,
Tomas Luyten
,
Jan B. Parys
,
Stefanie Weidtkamp‐Peters
,
Andrea Borchardt
,
Andreas S. Reichert
,
Aida Peña‐Blanco
,
Ana J. García‐Sáez
,
Samuel Itskanov
,
Alexander M. van der Bliek
,
Peter Proksch
,
Sebastian Wesselborg
,
Björn Stork
·
YOU?
·
· 2018
· Open Access
·
· DOI: https://doi.org/10.1038/s41419-018-0312-8
YOU?
·
· 2018
· Open Access
·
· DOI: https://doi.org/10.1038/s41419-018-0312-8
Mitochondria are cellular organelles with crucial functions in the generation and distribution of ATP, the buffering of cytosolic Ca 2+ and the initiation of apoptosis. Compounds that interfere with these functions are termed mitochondrial toxins, many of which are derived from microbes, such as antimycin A, oligomycin A, and ionomycin. Here, we identify the mycotoxin phomoxanthone A (PXA), derived from the endophytic fungus Phomopsis longicolla , as a mitochondrial toxin. We show that PXA elicits a strong release of Ca 2+ from the mitochondria but not from the ER. In addition, PXA depolarises the mitochondria similarly to protonophoric uncouplers such as CCCP, yet unlike these, it does not increase but rather inhibits cellular respiration and electron transport chain activity. The respiration-dependent mitochondrial network structure rapidly collapses into fragments upon PXA treatment. Surprisingly, this fragmentation is independent from the canonical mitochondrial fission and fusion mediators DRP1 and OPA1, and exclusively affects the inner mitochondrial membrane, leading to cristae disruption, release of pro-apoptotic proteins, and apoptosis. Taken together, our results suggest that PXA is a mitochondrial toxin with a novel mode of action that might prove a useful tool for the study of mitochondrial ion homoeostasis and membrane dynamics.
Related Topics
Concepts
Mitochondrion
Cell biology
Biology
Mitochondrial apoptosis-induced channel
Mitochondrial fission
Oligomycin
mitochondrial fusion
Cytosol
Mitochondrial carrier
Inner mitochondrial membrane
Biochemistry
Mitochondrial DNA
Bacterial outer membrane
ATPase
Gene
Escherichia coli
Enzyme
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1038/s41419-018-0312-8
- https://www.nature.com/articles/s41419-018-0312-8.pdf
- OA Status
- gold
- Cited By
- 34
- References
- 62
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W2792026916
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W2792026916Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1038/s41419-018-0312-8Digital Object Identifier
- Title
-
The mycotoxin phomoxanthone A disturbs the form and function of the inner mitochondrial membraneWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2018Year of publication
- Publication date
-
2018-02-19Full publication date if available
- Authors
-
Philip Böhler, Fabian Stuhldreier, Ruchika Anand, Arun Kumar Kondadi, David Schlütermann, Niklas Berleth, Jana Deitersen, Nora Hieke, Wenxian Wu, Marian Frank, Hendrik Niemann, Elisabeth Wesbuer, Andreas Barbian, Tomas Luyten, Jan B. Parys, Stefanie Weidtkamp‐Peters, Andrea Borchardt, Andreas S. Reichert, Aida Peña‐Blanco, Ana J. García‐Sáez, Samuel Itskanov, Alexander M. van der Bliek, Peter Proksch, Sebastian Wesselborg, Björn StorkList of authors in order
- Landing page
-
https://doi.org/10.1038/s41419-018-0312-8Publisher landing page
- PDF URL
-
https://www.nature.com/articles/s41419-018-0312-8.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://www.nature.com/articles/s41419-018-0312-8.pdfDirect OA link when available
- Concepts
-
Mitochondrion, Cell biology, Biology, Mitochondrial apoptosis-induced channel, Mitochondrial fission, Oligomycin, mitochondrial fusion, Cytosol, Mitochondrial carrier, Inner mitochondrial membrane, Biochemistry, Mitochondrial DNA, Bacterial outer membrane, ATPase, Gene, Escherichia coli, EnzymeTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
34Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 3, 2024: 7, 2023: 3, 2022: 6, 2021: 3Per-year citation counts (last 5 years)
- References (count)
-
62Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.protonophoric | 98 |
| abstract_inverted_index.respiration-dependent | 121 |
| cited_by_percentile_year.max | 99 |
| cited_by_percentile_year.min | 94 |
| countries_distinct_count | 3 |
| institutions_distinct_count | 25 |
| citation_normalized_percentile.value | 0.81457469 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |