The mitochondrial permeability transition in neurologic disease

M. D. Norenberg, K. V.Rama Rao

Research output: Contribution to journalArticle

117 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)983-997
Number of pages15
JournalNeurochemistry International
Volume50
Issue number7-8
DOIs
StatePublished - Jun 1 2007

Keywords

  • Alzheimer's disease
  • Ammonia
  • Amyotrophic lateral sclerosis
  • Apoptosis
  • Calcium homeostasis
  • Cell death
  • Cyclosporin A
  • Excitotoxicity
  • Hepatic encephalopathy
  • Huntington's disease
  • Ischemia
  • Manganese
  • Mitochondria
  • Mitochondrial permeability transition
  • Oxidative stress
  • Parkinson's disease
  • Reye's syndrome
  • Trauma

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Cellular and Molecular Neuroscience

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