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Three-dimensional Imaging and Analysis of Mitochondria within Human Intraepidermal Nerve Fibers
Published on: September 29, 2017
Mitochondrial pathways of neuronal necrosis
J Niquet1, D-W Seo, C G Wasterlain
1Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Biochemical Society Transactions
|November 1, 2006
Summary
Neuronal necrosis is an active, programmed process involving mitochondrial dysfunction and caspase activation. This programmed necrosis is triggered by energy failure or calcium overload during hypoxia or excitotoxicity.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Neuronal death mechanisms are crucial for understanding neurological disorders.
- Distinguishing between different forms of cell death, like necrosis and apoptosis, is vital.
- Mitochondria play a central role in regulating cell fate.
Purpose of the Study:
- To elucidate the mechanism of neuronal necrosis induced by hypoxia and excitotoxicity.
- To identify key molecular events and triggers involved in this specific form of neuronal death.
- To differentiate this process from other known cell death pathways.
Main Methods:
- Induction of neuronal necrosis using hypoxia and excitotoxicity models.
- Microscopic examination of cellular and subcellular changes, focusing on mitochondria.
- Analysis of molecular markers associated with cell death pathways, including cytochrome c and caspases.
Main Results:
- Neuronal necrosis was identified as an active, programmed process.
- Early mitochondrial swelling was observed, preceding other death events.
- Cytochrome c release and caspase cascade activation were key features of this necrosis.
- Energy failure and/or mitochondrial calcium overload were identified as potential triggers.
Conclusions:
- Neuronal necrosis can be a programmed event, termed 'programmed necrosis'.
- Mitochondrial integrity and function are critical in initiating this cell death pathway.
- The study highlights the role of mitochondrial death factors, including apoptosis-inducing factor, in programmed necrosis.
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