Drahota 2017 MiP2017

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Zdenek Drahota
Mitochondrial membrane permeability transition pore: function and regulation.

Link: MiP2017

Drahota Z, Endlicher R, Cervinkova Z (2017)

Event: MiP2017

COST Action MITOEAGLE
Mitochondrial Membrane permeability Transition Pore (MPTP) plays an important role in cell metabolism. It protects cells against oxidative stress induced by mitochondria when it operates in the reversible mode. When it is opened irreversibly, it triggers processes resulting in cell death. Up to now many factors, endogenous and exogenous, have been described that are involved in the regulation of its function [1]. However, our knowledge about its molecular structure, function and regulation is not yet sufficient. We tried, therefore, to get some new data characterizing functional activity and regulation of MPTP.

All experiments were performed on isolated liver mitochondria from adult male Wistar rats. Mitochondrial retention capacity for calcium (CRC) was evaluated using fluorescent membrane impermeable Ca-green by which we may follow Ca movements across the mitochodndrial membrane (fluorometer AMINCO-Bowman). The method of CRC measurement is based on sequential additions of small portions of calcium that are accumulated by mitochondria, till the moment when the critical concentration required for the pore opening is reached and all accumulated calcium is released. CRC is expressed as nmole Ca/mg protein required for full opening of the MPTP.

We present some new data about the regulation of the MPTP function obtained by the measurements of CRC. We observed that the CRC value is just an arbitrary value, that can be highly modified by the composition of the medium. Phosphate and t-BHP decreased CRC to 30% of control values and both to about 15% of control values. We found that the value of CRC is also dependent on the Ca concentration in sequential additions and on the amount of mitochondria in the medium. All these data are difficult to explain. They could indicate that MPTP is not a classical membrane pore as was suggested recently by Szabo and Zoratti [2]. They proposed that MPTP is just a hole in the membrane and that its opening can be modified by various factors that influence membrane properties. This could also explain why up to now there cannot be identified any specific membrane compound(s) forming the MPTP.


Bioblast editor: Kandolf G O2k-Network Lab: CZ Hradec Kralove Cervinkova Z, CZ Prague Houstek J


Labels: MiParea: mt-Membrane 

Stress:Permeability transition  Organism: Rat  Tissue;cell: Liver  Preparation: Isolated mitochondria 





Affiliations and support

Drahota Z(1,3), Endlicher R(1,2), Červinková Z(1)
  1. Dept Physiol, Fac Medicine, Hradec Králové, Charles Univ
  2. Dept Anatom, Fac Medicine, Hradec Králové, Charles Univ
  3. Inst Physiol, Academy Sciences Czech Republic, Prague, Czech Republic. - zdenek.drahota@fgu.cas.cz
This work was supported by research program: PROGRES Q40/02 and Inter-COST LTC17044.

References

  1. Drahota Z, Endlicher R, Stankova P, Rychtrmoc D, Milerova M, Červinková Z. (2012) Characterization of calcium, phosphate and peroxide interactions in activation of mitochondrial swelling using derivative of the swelling curves, J Bioenerg Biomembr 44:309-15
  2. Szabo I, Zoratti M (2014) Mitochondrial channels: ion fluxes and more. Physiol Rev 94:519-608.