Figure 1

Mitochondrial structure of motor neurons in mutant SOD1 transgenic mice and calcium load in microdomains in a cell culture model of motoneuron disease. (A) a, Shows abnormalities like dilated cristae (asterisk) and leaking outer membrane (indicated with arrow) in mitochondrion. (A) b, Swollen dendritic mitochondria with dilated and disorganized cristae (adapted from ref. 31). (B-D) The simultaneous measurement of cytosolic calcium (Fura-2) and mitochondrial calcium (Rhod-2) concentrations in WT and G93A transfected SH-SY5Y cells during FCCP-evoked mitochondrial Ca²⁺ release. (B) The kinetic profile of the FCCP-evoked Ca²⁺ release in the WT transfected SH-SY5Y neuroblastoma cells; the cytosolic (Error bar green, black square trace) and mitochondrial (Error bar red, black circle trace) compartment were measured simultaneously. The trace represents the mean of 5 cells in focus stimulated with 2 μM FCCP. (C) The corresponding kinetic profile of the FCCP-evoked Ca²⁺ release in the G93A transfected SH-SY5Y neuroblastoma cells; the cytosolic (Error bar green, black square trace) and mitochondrial (Error bar red, black circle trace) compartment were measured simultaneously. The trace represents the mean of 5 cells in focus stimulated with 2 μM FCCP. FCCP-evoked [Ca²⁺]mito signals were smaller in amplitude and exhibited slower kinetics in G93A transfected SH-SY5Y cells compared to WT transfected cells and were altered from [Ca²⁺]i efflux. (D) A bar diagram of the cytosolic (green bar) and mitochondrial (red bar) fluorescence signals (F/F0) from WT (F/F0 = 0.1569 ± 0.0235 for [Ca²⁺]i and F/F0 = −0.1069 ± 0.0181 for [Ca²⁺] mito; hollow; N = 5, n = 17) and G93A (F/F0 = 0.1008 ± 0.0248 for [Ca²⁺]i and F/F0 = −0.0486 ± 0.0043 for[Ca²⁺]mito; striped pattern, N = 4; n = 17) transfected SH-SY5Y neuroblastoma cells. Values represent means ± SD, **p < 0.001. N = Number of experiments; n = Number of cells (adapted from ref. 94).