Mitochondrial dysfunction

Birch-Machin, M.A., Jackson, S., Singh Kler, R.S., Turnbull, D.M. (1993). Smdy of skeletal muscle mitochondrial dysfunction. Methods Toxicol. 2, 51-69. 

The electrophysiological and neuropathological changes are similar to the axonal neuropathy and prominent loss of unmyelinated fibers seen in DSP (Simpson and Tagliati 1995). Although the specific pathological mechanisms of ATN are not fully known, there is abundant indirect evidence of mitochondrial dysfunction as a principal mechanism. Prominent mitochondrial disruption and cristae abnormalities... 

Shenker BJ, Guo TL, Shapiro IM. 1998. Low-level methylmercury exposure causes human T-cells to undergo apoptosis evidence of mitochondrial dysfunction. Environ Res 77 149-159. 

Terasaki, M., Asai, A., Zhang, H. and Nagao, A. 2007. A highly polar xanthophyll of 9 -cis-neoxanthin induces apoptosis in HCT116 human colon cancer cells through mitochondrial dysfunction. Mol Cell Biochem 300 227-237. 

Iron has been implicated in many neurodegenerative diseases, particularly microglia activation and mitochondrial dysfunction. 

PINK1 PTEN-induced putative kinase 1 lp36 Recessive Mitochondrial dysfunction ( )... 

Mitochondrial dysfunction produces syndromes involving mainly muscle and the central nervous system 706... 

What are the relationships of Lewy body formation, proteasomal protein degradation and mitochondrial dysfunction to parkinsonism (see ref. [8] for a detailed review). 

Adults require 1-2 mg of copper per day, and eliminate excess copper in bile and feces. Most plasma copper is present in ceruloplasmin. In Wilson s disease, the diminished availability of ceruloplasmin interferes with the function of enzymes that rely on ceruloplasmin as a copper donor (e.g. cytochrome oxidase, tyrosinase and superoxide dismutase). In addition, loss of copper-binding capacity in the serum leads to copper deposition in liver, brain and other organs, resulting in tissue damage. The mechanisms of toxicity are not fully understood, but may involve the formation of hydroxyl radicals via the Fenton reaction, which, in turn initiates a cascade of cellular cytotoxic events, including mitochondrial dysfunction, lipid peroxidation, disruption of calcium ion homeostasis, and cell death. 

Prabakaran, S., Swatton, J. E.,Ryan, M.M. etal. Mitochondrial dysfunction in schizophrenia evidence for compromised brain metabolism and oxidative stress. Mol. Psychiatry, 9 684-697, 2004. 

Pritsos, C.A. 1996. Mitochondrial dysfunction and energy depletion from subchronic peroral exposure to cyanide using the Wistar rat as a mammalian model. Toxic Subst. Meehan. 15 219-229. 

P Amyloid protein aggregation, leading to formation of plaques / Hyperphosphorylation of tau protein, leading to intracellular NFT development and collapse of microtubules / Inflammatory processes—levels of multiple cytokines and chemokines are elevated in AD brains / Neurovasculature dysfunction / Oxidative stress / Mitochondrial dysfunction... 

Green PS, Leeuwenburgh C (2002) Mitochondrial dysfunction is an early indicator of doxorubicin-induced apoptosis. Biochimica et Biophysica Acta-Molecular Basis of Disease 1588 94-101. 

Oxidized LDL alter cellular functions role in cell death Oxidized LDL seem to be poorly degraded by lysosomal enzymes and accumulate in lysosomes altering in turn their functionality (Dean et al., 1997). It has been proposed that inhibition of oxidized LDL degradation and subsequent lipid accumulation may induce a destabilization of the acidic compartment, and lysosomal rupture with a relocation of lysosomal enzymes in the cytosol (li W et al, 1998). This process, also called endopepsis , occurs early and could precede mitochondrial dysfunction and cell death (Lossel et al., 1994). Moreover, oxidized LDL trigger a dysfunction of the intracellular proteolytic ubiquitin/proteasome pathway (early activation followed by inhibition)... 

Shimizu, S., Eguchi, Y., Kanuike, W., Funahashi, Y., Mignon, A., Lacronique, V., Matsuda, H., and Tsujimoto, Y., 1998, Bcl-2 prevents apoptotic mitochondrial dysfunction by regulating proton flux, Proc.Natl.Acad.Sci. U.S.A. 95 1455-1459. 

Figure 2. Mechanisms and signalings of neuronal death. Death can be initiated at the membrane by activation of death domain receptors (DDR), or by intracellular signalings through oxidative stress (and the production of reactive oxigen species, ROS), perturbed calcium homeostasis, mitochondrial dysfunction (release of cytochrome c, cytC), activation of caspases, as well as reactivation of cell cycle genes such as the transcription factor E2F (see text). Interconnections have been demonstrated (dotted lines) depending on the apoptotic context...

The underlying cause of mitochondrial dysfunction can be investigated in muscle using mitochondria isolated from a biopsy sample. They are incubated with different substrates and the oxygen consumption is measured. Defects in complexes 1, 111 or IV can be identihed in this way (Appendix 9.9). 

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