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

Paul S. Brookes, Yisang Yoon, James L. Robotham, M. W. Anders, Shey Shing Sheu

Research output: Contribution to journalReview article

1431 Citations (Scopus)

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 Ca2+ homeostasis is now recognized to play a key role in several pathologies. For example, mitochondrial matrix Ca2+ 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 Ca2+ and mitochondrial dysfunction in disease, the molecular mechanisms by which Ca2+ can elicit mitochondrial dysfunction remain elusive. This review highlights the delicate balance between the positive and negative effects of Ca2+ and the signaling events that perturb this balance. Overall, a "two-hit" hypothesis is developed, in which Ca2- plus another pathological stimulus can bring about mitochondrial dysfunction.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume287
Issue number4 56-4
DOIs
StatePublished - Oct 1 2004

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Hate
Love
Adenosine Triphosphate
Calcium
Mitochondria
Pathology
Cytochromes c
Organelles
Energy Metabolism
Permeability
Reactive Oxygen Species
Homeostasis
Apoptosis

Keywords

  • Apoptosis
  • Free radicals
  • Ischemia
  • Mitochondria
  • Neurodegeneration
  • Permeability transition
  • Reactive oxygen species

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

Cite this

Calcium, ATP, and ROS : A mitochondrial love-hate triangle. / Brookes, Paul S.; Yoon, Yisang; Robotham, James L.; Anders, M. W.; Sheu, Shey Shing.

In: American Journal of Physiology - Cell Physiology, Vol. 287, No. 4 56-4, 01.10.2004.

Research output: Contribution to journalReview article

Brookes, Paul S. ; Yoon, Yisang ; Robotham, James L. ; Anders, M. W. ; Sheu, Shey Shing. / Calcium, ATP, and ROS : A mitochondrial love-hate triangle. In: American Journal of Physiology - Cell Physiology. 2004 ; Vol. 287, No. 4 56-4.
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