The role of mitochondria in status epilepticus

Abstract

Reflecting their central roles in cellular metabolism,including energy production and calcium homeostasis, mi-tochondria have been proposed to act as the “stress sensor”of the cell, and in extreme circumstances (e.g., excitotoxi-city) the executioner. A large body of work has establishedmitochondrial dysfunction as the “lowest common denom-inator” in a range of inherited (Kwong et al., 2006) and ac-quired (Cock, 2005) neurodegenerative disease processes.In addition to bioenergetic failure and increased cytosoliccalcium, consequences of impaired mitochondrial func-tion (summarized in Fig. 1) include oxidative stress (ex-cessive free radical production and impaired synthesis ofantioxidants, especially glutathione), and the release ofkey proteins into the cytosol (mitochondrial permeabilitytransition) triggering cell death pathways (caspases). How-ever, it is also increasingly clear that many of the “patho-logical” processes also have key physiological roles inmetabolic control and cell signaling, in which context pro-teins such as uncoupling proteins have attracted particu-lar interest, but are not yet fully understood (Cock, 2005).On this background, interest in the role of mitochondriain seizure-related brain damage has rapidly developed overthe last decade; though only work specifically relating tostatus epilepticus (as opposed to chronic epilepsy) will bediscussed here.