TY - JOUR
T1 - Regulation of mitochondrial Ca2+ and its effects on energetics and redox balance in normal and failing heart
AU - Liu, Ting
AU - O'Rourke, Brian
N1 - Funding Information:
Acknowledgements This work was supported by NIH grant P01 HL081427.
PY - 2009/4
Y1 - 2009/4
N2 - Ca2+ has been well accepted as a signal that coordinates changes in cytosolic workload with mitochondrial energy metabolism in cardiomyocytes. During increased work, Ca2+ is accumulated in mitochondria and stimulates ATP production to match energy supply and demand. The kinetics of mitochondrial Ca2+ ([Ca2+]m) uptake remains unclear, and we review the debate on this subject in this article. [Ca 2+]m has multiple targets in oxidative phosphorylation including the F1/FO ATPase, the adenine nucleotide translocase, and Ca 2+-sensitive dehydrogenases (CaDH) of the tricarboxylic acid (TCA) cycle. The well established effect of [Ca2+]m is to activate CaDHs of the TCA cycle to increase NADH production. Maintaining NADH level is not only critical to keep a high oxidative phosphorylation rate during increased cardiac work, but is also necessary for the reducing system of the cell to maintain its reactive oxygen species (ROS) -scavenging capacity. Further, we review recent data demonstrating the deleterious effects of elevated Na+ in cardiac pathology by blunting [Ca2+]m accumulation.
AB - Ca2+ has been well accepted as a signal that coordinates changes in cytosolic workload with mitochondrial energy metabolism in cardiomyocytes. During increased work, Ca2+ is accumulated in mitochondria and stimulates ATP production to match energy supply and demand. The kinetics of mitochondrial Ca2+ ([Ca2+]m) uptake remains unclear, and we review the debate on this subject in this article. [Ca 2+]m has multiple targets in oxidative phosphorylation including the F1/FO ATPase, the adenine nucleotide translocase, and Ca 2+-sensitive dehydrogenases (CaDH) of the tricarboxylic acid (TCA) cycle. The well established effect of [Ca2+]m is to activate CaDHs of the TCA cycle to increase NADH production. Maintaining NADH level is not only critical to keep a high oxidative phosphorylation rate during increased cardiac work, but is also necessary for the reducing system of the cell to maintain its reactive oxygen species (ROS) -scavenging capacity. Further, we review recent data demonstrating the deleterious effects of elevated Na+ in cardiac pathology by blunting [Ca2+]m accumulation.
KW - Cardiac energy metabolism
KW - Heart failure
KW - Mitochondrial Ca handling
KW - Oxidative phosphorylation
KW - Redox balance
UR - http://www.scopus.com/inward/record.url?scp=67650688732&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67650688732&partnerID=8YFLogxK
U2 - 10.1007/s10863-009-9216-8
DO - 10.1007/s10863-009-9216-8
M3 - Short survey
C2 - 19390955
AN - SCOPUS:67650688732
SN - 0145-479X
VL - 41
SP - 127
EP - 132
JO - Journal of Bioenergetics and Biomembranes
JF - Journal of Bioenergetics and Biomembranes
IS - 2
ER -