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Review
. 2013 Oct 28:2013:180759.
doi: 10.1155/2013/180759. eCollection 2013.

Mitochondrial quality control: decommissioning power plants in neurodegenerative diseases

Rukmini Mukherjee  1 , Oishee Chakrabarti
Affiliations
Review

Mitochondrial quality control: decommissioning power plants in neurodegenerative diseases

Rukmini Mukherjee et al. ScientificWorldJournal. .

Abstract

The cell has an intricate quality control system to protect its mitochondria from oxidative stress. This surveillance system is multi-tiered and comprises molecules that are present inside the mitochondria, in the cytosol, and in other organelles like the nucleus and endoplasmic reticulum. These molecules cross talk with each other and protect the mitochondria from oxidative stress. Oxidative stress is a fundamental part of early disease pathogenesis of neurodegenerative diseases. These disorders also damage the cellular quality control machinery that protects the cell against oxidative stress. This exacerbates the oxidative damage and causes extensive neuronal cell death that is characteristic of neurodegeneration.

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Figures

Figure 1
Figure 1
Mitochondrial changes in neurodegeneration. Most neurodegenerative diseases result in defects in oxidative phosphorylation, respiratory dysfunction, increased ROS production, lowered mitochondrial membrane potential, decrease in synthesis of antioxidants, mtDNA mutations, impaired protein import, increased fragmentation of mitochondria, and activation of mitophagy and apoptosis. Sources of reactive oxygen species are marked by red stars. Abbreviations: Htt, Huntingtin; Ub, ubiquitin; ΔΨ, membrane potential; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; ROS, reactive oxygen species; mtDNA, mitochondrial DNA; Aβ, amyloid beta; APP, amyloid precursor protein; TIM, translocase of inner membrane; TOM, translocase of outer membrane; SOD1, superoxide dismutase 1; VDAC, voltage dependent anion channel; ANT, adenine nucleotide translocator; Pink1, PTEN-induced putative kinase 1; αKGDH, alpha ketoglutarate dehydrogenase; cyt c, cytochrome c.
Figure 2
Figure 2
The intramitochondrial quality control system. The intraorganellar quality control system comprises antioxidant enzymes, molecular chaperones, and proteases found in all compartments of the mitochondria. OM, mitochondrial outer membrane; IM, mitochondrial inner membrane; IMS, intermembrane space.
Figure 3
Figure 3
Integrated response of the cell to oxidative stress. In oxidative stress, the mitochondrial quality control works in sync with other cellular defences like the ubiquitin proteasomal system and the autophagy machinery. This involves interorganellar cross talk of the mitochondria with the endoplasmic reticulum and the nucleus. Failure of quality control systems leads to activation of apoptosis.
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