Multifaceted deaths orchestrated by mitochondria in neurones

Phillip Nagley, Gavin C. Higgins, Julie D. Atkin, Philip M. Beart

Research output: Contribution to journalReview articleResearchpeer-review

Abstract

Neurones undergo diverse forms of cell death depending on the nature and severity of the stress. These death outcomes are now classified into various types of programmed cell death, including apoptosis, autophagy and necrosis. Each of these pathways can run in parallel and all have mitochondria as a central feature. Recruitment of mitochondria into cell death signalling involves either (or both) induction of specific death responses through release of apoptogenic proteins into the cytosol, or perturbation in function leading to loss of mitochondrial energisation and ATP synthesis. Cross-talk between these signalling pathways, particularly downstream of mitochondria, determines the resultant pattern of cell death. The differential recruitment of specific death pathways depends on the timing of engagement of mitochondrial signalling. Other influences on programmed cell death pathways occur through stress of the endoplasmic reticulum and the associated ubiquitin-proteasome system normally handling potentially neurotoxic protein aggregates. Based upon contemporary evidence apoptosis is a relatively rare in the mature brain whereas the contribution of programmed necrosis to various neuropathologies has been underestimated. The death outcomes that neurones exhibit during acute or chronic injury or pathological conditions considered here (oxidative stress, hypoxic-ischaemic injury, amyotrophic lateral sclerosis, Parkinson's and Huntington's diseases) fall within a spectrum of the diverse death types across the apoptosis-necrosis continuum. Indeed, dying or dead neurones may simultaneously manifest characteristics of more than one type of death pathway. Understanding neuronal death pathways and their cross-talk not only informs the detailed pathobiology but also suggests novel therapeutic strategies.

LanguageEnglish
Pages167-185
Number of pages19
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1802
Issue number1
DOIs
Publication statusPublished - Jan 2010
Externally publishedYes

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Mitochondria
Neurons
Cell Death
Necrosis
Apoptosis
Endoplasmic Reticulum Stress
Huntington Disease
Autophagy
Wounds and Injuries
Amyotrophic Lateral Sclerosis
Proteasome Endopeptidase Complex
Ubiquitin
Cytosol
Parkinson Disease
Oxidative Stress
Adenosine Triphosphate
Brain
Proteins

Cite this

Nagley, Phillip ; Higgins, Gavin C. ; Atkin, Julie D. ; Beart, Philip M. / Multifaceted deaths orchestrated by mitochondria in neurones. In: Biochimica et Biophysica Acta - Molecular Basis of Disease. 2010 ; Vol. 1802, No. 1. pp. 167-185.
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Multifaceted deaths orchestrated by mitochondria in neurones. / Nagley, Phillip; Higgins, Gavin C.; Atkin, Julie D.; Beart, Philip M.

In: Biochimica et Biophysica Acta - Molecular Basis of Disease, Vol. 1802, No. 1, 01.2010, p. 167-185.

Research output: Contribution to journalReview articleResearchpeer-review

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