Swelling of mitochondria in cultured rat hippocampal astrocytes is induced by high cytosolic Ca2+ load, but not by mitochondrial depolarization

FEBS Letters

Reiser, Georg¹  Kahlert, Stefan¹ 

[1]Medizinische Fakultät der Otto-von-Guericke-Universität Magdeburg, Institut für Neurobiochemie, Leipziger Str. 44, 39120 Magdeburg, Germany

关键词: Mitochondrial potential;    Mitochondrial morphology;    Permeability transition pore;    Calcium homeostasis;    Apoptosis;    PTP;    permeability transition pore;    FCCP;    carbonyl cyanide p-(trifluoro)methoxyphenylhydrazone;    TMRE;    tetramethylrhodamine ethyl ester perchlorate;    GFAP;    glial fibrillary acidic protein;    HBSS;    Hanks’ buffered salt solution;    CsA;    cyclosporin A;   

DOI  :  10.1016/S0014-5793(02)03394-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The influence of cytosolic Ca²⁺ load and of mitochondrial membrane potential change on mitochondrial morphology was investigated in cultured rat hippocampal astrocytes. The uncoupler FCCP, applied together with oligomycin, depolarized mitochondria rapidly but did not change their morphology. Depolarization was associated with a moderate cytosolic [Ca²⁺]_i rise of up to 0.3 μM. Only high cytosolic Ca²⁺ load (above a threshold of 50 μM), which was evoked by application of the ionophore 4-Br-A23187 in Ca²⁺-containing medium, caused drastic change of mitochondrial morphology. The shape change from the typical rod-like to a spherical shape, indicating mitochondrial swelling, was associated with depolarization. Cyclosporin A sensitivity suggests involvement of permeability transition. Thus, a dramatic cytosolic [Ca²⁺]_i rise is required to induce mitochondrial swelling and depolarization. A large but still moderate [Ca²⁺]_i rise evoked by physiological stimulation, however, has no comparable effect.

【 授权许可】

Unknown