The mitochondrial permeability transition in neurologic disease

Neurochem Int. 2007 Jun;50(7-8):983-97. doi: 10.1016/j.neuint.2007.02.008. Epub 2007 Mar 4.


Mitochondria, being the principal source of cellular energy, are vital for cell life. Yet, ironically, they are also major mediators of cell death, either by necrosis or apoptosis. One means by which these adverse effects occur is through the mitochondrial permeability transition (mPT) whereby the inner mitochondrial membrane suddenly becomes excessively permeable to ions and other solutes, resulting in a collapse of the inner membrane potential, ultimately leading to energy failure and cell necrosis. The mPT may also bring about the release of various factors known to cause apoptotic cell death. The principal factors leading to the mPT are elevated levels of intracellular Ca2+ and oxidative stress. Characteristically, the mPT is inhibited by cyclosporin A. This article will briefly discuss the concept of the mPT, its molecular composition, its inducers and regulators, agents that influence its activity and describe the consequences of its induction. Lastly, we will review its potential contribution to acute neurological disorders, including ischemia, trauma, and toxic-metabolic conditions, as well as its role in chronic neurodegenerative conditions such as Alzheimer's disease, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Alzheimer Disease / etiology
  • Alzheimer Disease / physiopathology
  • Calcium / physiology
  • Energy Metabolism
  • Humans
  • Huntington Disease / physiopathology
  • Hyperglycemia / physiopathology
  • Manganese / toxicity
  • Mitochondrial Membranes / physiology*
  • Mitochondrial Swelling / physiology
  • Motor Neuron Disease / physiopathology
  • Nervous System Diseases / etiology
  • Nervous System Diseases / physiopathology*
  • Neurodegenerative Diseases / etiology
  • Neurodegenerative Diseases / physiopathology
  • Neurotoxins / toxicity
  • Parkinsonian Disorders / etiology
  • Parkinsonian Disorders / physiopathology
  • Permeability


  • Neurotoxins
  • Manganese
  • Calcium