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a
b
*
F
N
Space
15
µ
m
Time
100 s
Fig. 5.4 Cell-wide synchronized mitochondrial oscillations after local generation of ROS.
(a) Cardiomyocyte loaded at 37
C with tetramethylrhodamine ethyl ester (TMRE,
ΔΨ
m
indicator,
upper images
) and 5-(-6)-chloromethyl-2, 7-dichlorohydrofluorescein diacetate (CM-H
2
DCFH,
ROS-sensitive, lower images). By using two-photon laser excitation, and after 10-20 control
images were collected, a small region of a cardiac myocyte (20
20 pixels) was excited in a
single flash resulting in rapid loss of mitochondrial membrane potential,
ΔΨ
m
(a,
white square
in
upper left
; b,
white arrow
) and local generation of ROS (a,
white square
in
lower left
). Thereafter,
ΔΨ
m
remained depolarized in the
flashed area
throughout the experiment (see b). The
right
images
in a show the first whole-cell
ΔΨ
m
depolarization (b,
asterisk
) after a delay time.
(b) Time-line image of TMRE created by analyzing a line drawn along the longitudinal axis
of the cell (shown in a,
upper left
). The
arrow
points out the timing of the flash and the
brackets point out the flash region (
Upper
) and the nucleus (
Lower
). The synchronous
ΔΨ
m
mitochondrial oscillations are evident as vertical
blue bands
. The mitochondria that do not
belong to the spanning cluster remained visibly polarized. Reproduced from Aon MA, Cortassa S,
and O'Rourke B. (2004) PNAS 101, 4447-4452
energetics oscillates. Under these conditions the performance mode of mitochon-
drial function becomes a key arbiter of life and death at cellular and organ levels
(Aon et al.
2006a
; Gustafsson and Gottlieb
2008
; O'Rourke et al.
2005
). The idea
that mitochondria could function as a coordinated network of oscillators emerged
from studies in living cardiomyocytes subjected to metabolic stress (Aon
et al.
2003
,
2004a
,
2006b
).
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