Projects per year
Fusaricidins and related LI-F compounds are effective bactericides and fungicides. Recently, we have found that they are highly toxic to mammalian cells. Here, we studied the effect of fusaricidin-type compounds (FTCs) on the membranes of mammalian cells. Ethanol extracts from Paenibacillus polymyxa strains, RS10 and I/Sim, were fractionated and analyzed by HPLC and mass spectrometry. The effects of FTCs on mitochondrial functions and integrity were studied by standard methods: measurements of swelling, membrane potential (ΔΨm), respiration rate, cytochrome c release, and pore sizes. Superoxide flashes were registered by 3,7-dihydro-2-methyl-6-(4-methoxyphenyl)imidazol[1,2-a]pyrazine-3-one (MCLA). Plasma membrane permeability was assessed by propidium iodide (PI) staining and ATP release. FTCs caused the permeabilization of the inner mitochondria membrane (IMM) to ions and low-molecular-weight (~750 Da) solutes. The permeabilization did not depend on the permeability transition pore (mPTP) but was strongly dependent on ΔΨm. Fusaricidins A plus B, LI-F05a, and LI-F05b-LI-F07b permeabilized IMM with comparable efficiency. They created pores and affected mitochondrial functions and integrity similarly to mPTP opening. They permeabilized the sperm cell plasma membrane to ATP and PI. Thus, the formation of pores in polarized membranes underlays the toxicity of FTCs to mammals. Besides, FTCs appeared to be superior reference compounds for mPTP studies.
|Publication status||Published - 1 Sep 2019|
|MoE publication type||A1 Journal article-refereed|
- LI-F compounds
- permeability transition pore
- plasma membrane
FingerprintDive into the research topics of 'Fusaricidin-Type Compounds Create Pores in Mitochondrial and Plasma Membranes of Mammalian Cells'. Together they form a unique fingerprint.
- 2 Finished
Mikkola, R., Salonen, H., Alapieti, T., Järvi, K. & Castagnoli, E.
01/03/2016 → 31/12/2018
Project: Business Finland: Other research funding
Toxin transport mechanisms from moisture damaged structures to indoor air
Castagnoli, E., Kurnitski, J., Mikkola, R., Ahmed, K., Piironen, J., Andersson, A., Taebnia, M., Alapieti, T., Järvi, K., Salonen, H. & Vornanen-Winqvist, C.
01/09/2015 → 31/08/2019
Project: Academy of Finland: Other research funding