Protein kinases reduce mitochondrial Ca2+ uptake through an action on the outer mitochondrial membrane.

  • Szanda G
  • Halász E
  • Spät A
  • 1


    Mendeley users who have this article in their library.
  • N/A


    Citations of this article.


Cytosolic Ca(2+) signal induces mitochondrial Ca(2+) uptake that has far-reaching effect on several cellular functions. We have previously shown in H295R cells that the transfer of cytosolic Ca(2+) signal into mitochondria is attenuated by the simultaneous activation of p38 MAPK and novel-type PKC isoforms (Szanda et al. (2008) [1], Koncz et al. (2009) [2]). In the present study we show that (i) kinase-mediated inhibition of mitochondrial Ca(2+) uptake persists after clamping or dissipation of the mitochondrial membrane potential; (ii) kinase activation increases the [Ca(2+)] required for half-maximal Ca(2+) uptake rate in permeabilized cells; (iii) inhibition of the Ca(2+) uptake by the kinases is dependent on an intact mitochondrial outer membrane; (iv) when p38 MAPK and novel-type PKC isoforms are activated, the outer mitochondrial membrane may limit Ca(2+) diffusion even in the low micromolar [Ca(2+)] range. These findings confirm the concept that the outer mitochondrial membrane impedes mitochondrial Ca(2+) uptake by reducing the availability of Ca(2+) at the transport sites (i.e. the inner mitochondrial membrane), and suggest that Ca(2+) transport through the outer membrane is controlled by the activity of p38 MAPK and novel-type PKC isoforms.

Author-supplied keywords

  • Animals
  • Calcium
  • Calcium Signaling
  • Calcium Signaling: physiology
  • Calcium: antagonists & inhibitors
  • Calcium: metabolism
  • Cell Line
  • Down-Regulation
  • Down-Regulation: physiology
  • Enzyme Activation
  • Enzyme Activation: physiology
  • Humans
  • Isoenzymes
  • Isoenzymes: physiology
  • MAP Kinase Signaling System
  • MAP Kinase Signaling System: physiology
  • Membrane Potential
  • Mitochondria
  • Mitochondria: enzymology
  • Mitochondria: metabolism
  • Mitochondrial
  • Mitochondrial Membranes
  • Mitochondrial Membranes: enzymology
  • Mitochondrial Membranes: metabolism
  • Mitochondrial: physiology
  • Protein Kinase C
  • Protein Kinase C: metabolism
  • Protein Kinase C: physiology
  • p38 Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases: metabolism
  • p38 Mitogen-Activated Protein Kinases: physiology

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document


  • Gergö Szanda

  • Eszter Halász

  • András Spät

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free