Calcium, ATP, and ROS: a mitochondrial love-hate triangle - PubMed (original) (raw)

Review

. 2004 Oct;287(4):C817-33.

doi: 10.1152/ajpcell.00139.2004.

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Review

Calcium, ATP, and ROS: a mitochondrial love-hate triangle

Paul S Brookes et al. Am J Physiol Cell Physiol. 2004 Oct.

Free article

Abstract

The mitochondrion is at the core of cellular energy metabolism, being the site of most ATP generation. Calcium is a key regulator of mitochondrial function and acts at several levels within the organelle to stimulate ATP synthesis. However, the dysregulation of mitochondrial Ca(2+) homeostasis is now recognized to play a key role in several pathologies. For example, mitochondrial matrix Ca(2+) overload can lead to enhanced generation of reactive oxygen species, triggering of the permeability transition pore, and cytochrome c release, leading to apoptosis. Despite progress regarding the independent roles of both Ca(2+) and mitochondrial dysfunction in disease, the molecular mechanisms by which Ca(2+) can elicit mitochondrial dysfunction remain elusive. This review highlights the delicate balance between the positive and negative effects of Ca(2+) and the signaling events that perturb this balance. Overall, a "two-hit" hypothesis is developed, in which Ca(2+) plus another pathological stimulus can bring about mitochondrial dysfunction.

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