Fusaricidin-Type Compounds Create Pores in Mitochondrial and Plasma Membranes of Mammalian Cells
Abstract
:1. Introduction
2. Materials and Methods
2.1. Reagents
2.2. Sperm Cells
2.3. Paenibacillus Polymyxa Strains
2.4. HPLC and Mass Spectrometry Analysis
2.5. Isolation and Purification of Rat Liver Mitochondria
2.6. Recording of the Permeabilization of Mitochondrial Membranes
2.7. Assessment of Membrane Potential (ΔΨm)
2.8. Measurements of the Rate of Oxygen Consumption by Isolated Mitochondria
2.9. Registration of Superoxide Anion Production
2.10. Measurement of the Release of Cytochrome C From Mitochondria
2.11. Measurement of the Size of Pores in the Mitochondrial Inner Membrane
2.12. Assay of the Toxicity of Fusaricidins to Sperm Cells
2.13. Measurement of ATP Release from Sperm Cells
2.14. Statistical Analysis
3. Results
3.1. RS10 and I/Sim Extracts Induce Mitochondrial Swelling
3.2. RS10 Extract Permeabilizes Mitochondrial Membranes in an mPTP-Independent and ΔΨm-Dependent Manner
3.3. Content of Fusaricidin-Type Compounds in RS10 and I/Sim Extracts
3.4. Mitochondrial Swelling Induced by Purified FTCs from RS10 and I/Sim Extracts
3.5. Effects of FTCs on Mitochondrial Functions and Integrity
3.6. FTCs Cause Fast Permeabilization of Plasma Membrane to Low-Molecular-Weight Solutes
4. Discussion
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
ΔΨm | mitochondrial inner membrane potential |
BSA | bovine serum albumin |
CsA | cyclosporin A |
EGTA | ethylene glycol-bis(2-aminoethylether)-N,N,N′,N′-tetraacetic acid |
FCCP | carbonyl cyanide p-(trifluoromethoxy)phenyl-hydrazone |
FTC | fusaricidin-type compound |
HEPES | 4-(2-hydroxyethyl)piperazine-1-ethanesulfonic acid |
IMM | inner mitochondria membrane |
JC-1 | 5,5′,6,6′-Tetrachloro-1,1´,3,3′’-tetraethylbenzimidazolylcarbocyanine iodide |
MCLA | 7-dihydro-2-methyl-6-(4-methoxyphenyl)imidazol[1,2-a]pyrazine-3-one |
MDCL | MCLA-derived chemiluminescence |
mPTP | mitochondrial permeability transition pore |
PI | propidium iodide |
PEG | polyethylene glycol |
TMPD | N,N,N’N’-tetramethyl-p-phenylenediamide |
TPP+ | tetraphenylphosphonium chloride |
Appendix A
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Number of Toxic HPLC Fraction | Compound * | Mass Ion [M + H]+ m/z |
---|---|---|
1 | Fusaricidin C | 947.7 |
Fusaricidin D | 961.6 | |
2 | Fusaricidin A | 883.7 |
Fusaricidin B | 897.6 | |
3 | LI-F05a | 897.6 |
LI-F06b/LI-F05b | 911.6 | |
LI-F07b | 945.5 | |
LI-F07a | 931.6 | |
4 | LI-F06b/LI-F05b and LI-F07b | 911.6 and 945.6 |
LI-F08b | 925.6 | |
Fusaricidin/LI-F ** | 960.5 |
1-h Incubation | Motility | ΔΨm (JC1 Staining) | PM Permeability (PI Staining) |
---|---|---|---|
Control | ≥60% | ≥98% | ≤5% |
Ethanol (0.5%) | ≥60% | ≥98% | ≤5% |
RS10 (µg/mL) 50 | 1–2% | 1–2% | >90% |
25 | ~10% | 5–10% | ~60% |
12.5 | ~40% | 30–40% | 30–40% |
6.25 | ~50% | 40–50% | ≤20% |
A+B (9.35 µg/mL) | 1–2% | 1–2% | ~90% |
LI-F05a (5.06 µg/mL) | 5–10% | 5–10% | ≥70% |
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Mikkola, R.; Andersson, M.; Kharechkina, E.; Kruglova, S.; Kruglov, A. Fusaricidin-Type Compounds Create Pores in Mitochondrial and Plasma Membranes of Mammalian Cells. Biomolecules 2019, 9, 433. https://doi.org/10.3390/biom9090433
Mikkola R, Andersson M, Kharechkina E, Kruglova S, Kruglov A. Fusaricidin-Type Compounds Create Pores in Mitochondrial and Plasma Membranes of Mammalian Cells. Biomolecules. 2019; 9(9):433. https://doi.org/10.3390/biom9090433
Chicago/Turabian StyleMikkola, Raimo, Maria Andersson, Ekaterina Kharechkina, Svetlana Kruglova, and Alexey Kruglov. 2019. "Fusaricidin-Type Compounds Create Pores in Mitochondrial and Plasma Membranes of Mammalian Cells" Biomolecules 9, no. 9: 433. https://doi.org/10.3390/biom9090433