The most distinguishing feature of neurons is their capacity for regenerative electrical activity. This activity imposes a significant mitochondrial burden, especially in neurons that are autonomously active, have broad action potentials, and exhibit prominent Ca2+ entry.
Many of the genetic mutations and toxins associated with Parkinson’s disease compromise mitochondrial function, providing a mechanistic explanation for the pattern of neuronal pathology in this disease.
Because much of the neuronal mitochondrial burden can be traced to L-type voltage-dependent channels (channels for which there are brain-penetrant antagonists approved for human use), a neuroprotective strategy to reduce this burden is available.
↵* This work was supported, in whole or in part, by National Institutes of Health Grants NS047085, RR025355, and HL35440. This work was also supported by grants from the Hartman Foundation and the United States Army Medical Research and Materiel Command. This article is part of the Thematic Minireview Series on Calcium Function and Disease.
- © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.
- Soluble, Prefibrillar α-Synuclein Oligomers Promote Complex I-dependent, Ca2+-induced Mitochondrial Dysfunction
- Calcium Entry through L-type Calcium Channels Causes Mitochondrial Disruption and Chromaffin Cell Death
- Impaired Regulation of Brain Mitochondria by Extramitochondrial Ca2+ in Transgenic Huntington Disease Rats
- Mitochondrial Ca2+ Uptake from Plasma Membrane Cav3.2 Protein Channels Contributes to Ischemic Toxicity in PC12 Cells
- Mitochondrial Uncoupling Protein-4 Regulates Calcium Homeostasis and Sensitivity to Store Depletion-induced Apoptosis in Neural Cells