Mitochondrial Ca2+ dynamics reveals limited intramitochondrial Ca2+ diffusion

Akos A. Gerencser, V. Ádám-Vizi

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

To reveal heterogeneity of mitochondrial function on the single-mitochondrion level we have studied the spatiotemporal dynamics of the mitochondrial Ca2+ signaling and the mitochondrial membrane potential using wide-field fluorescence imaging and digital image processing techniques. Here we demonstrate first-time discrete sites-intramitochondrial hotspots-of Ca2+ uptake after Ca2+ release from intracellular stores, and spreading of Ca2+ rise within the mitochondria. The phenomenon was characterized by comparison of observations in intact cells stimulated by ATP and in plasma membrane permeabilized or in ionophore-treated cells exposed to elevated buffer [Ca2+]. The findings indicate that Ca2+ diffuses laterally within the mitochondria, and that the diffusion is limited for shorter segments of the mitochondrial network. These observations were supported by mathematical simulation of buffered diffusion. The mitochondrial membrane potential was investigated using the potentiometric dye TMRM. Irradiation-induced fluctuations (flickering) of TMRM fluorescence showed synchronicity over large regions of the mitochondrial network, indicating that certain parts of this network form electrical syncytia. The spatial extension of these syncytia was decreased by 2-aminoethoxydiphenyl borate (2-APB) or by propranolol (blockers of nonclassical mitochondrial permeabilities). Our data suggest that mitochondria form syncytia of electrical conductance whereas the passage of Ca2+ is restricted to the individual organelle.

Original languageEnglish
Pages (from-to)698-714
Number of pages17
JournalBiophysical Journal
Volume88
Issue number1
DOIs
Publication statusPublished - Jan 2005

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Mitochondrial Dynamics
Mitochondria
Giant Cells
Mitochondrial Membrane Potential
Optical Imaging
Ionophores
Propranolol
Organelles
Permeability
Buffers
Coloring Agents
Adenosine Triphosphate
Fluorescence
Cell Membrane

ASJC Scopus subject areas

  • Biophysics

Cite this

Mitochondrial Ca2+ dynamics reveals limited intramitochondrial Ca2+ diffusion. / Gerencser, Akos A.; Ádám-Vizi, V.

In: Biophysical Journal, Vol. 88, No. 1, 01.2005, p. 698-714.

Research output: Contribution to journalArticle

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