Mitochondria and Xxxxxxxxx’x Disease Sample Clauses

Mitochondria and Xxxxxxxxx’x Disease. In 1976, a chemistry student called Xxxxx Xxxxxxx synthesised the drug 1-methyl-4-phenyl- 4-propionoxy-piperidine (MPPP) for recreational use. However, the drug was contaminated with 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) and Kidston developed parkinsonian symptoms as a result. A few years later, in 1982, another six people were diagnosed with Parkinsonism after having intravenously injected the illicit drug MPPP. The neurologist X. Xxxxxxx Xxxxxxxx identified MPTP as a major contaminant in the substance, and further studied the effects of the drug on primates. This led to the discovery that MPTP metabolite 1-methyl-4-phenylpyridinium (MPP+) is primarily toxic to the dopamine- producing substantia nigra cells in the brain, where it interferes with complex I of the ETC. Later studies further investigated the structure and function of mitochondrial respiratory chain complexes in PD post-mortem tissue, and found a reduced complex I activity in the SNpc of PD patient tissue (Xxxxxxxx et al., 1990a; Xxxxxxxx et al., 1990b; Xxxxxxx et al., 1991; Xxxx et al., 1992; Xxxxxxxx et al., 1994; Xxxxxxxx et al., 2005). Studies have also reported the presence of multiple mtDNA deletions in the SNpc of PD patients. These somatic mtDNA mutations accumulate to an extent which leads to respiratory chain deficiency and eventual neuronal loss (Xxxxxx et al., 2006; Xxxxxxxxxx et al., 2006). Furthermore, loss of activity of the previously discussed PINK1 and Xxxxxx has been suggested to be implicated in respiratory chain deficits, particularly in Complex I dysfunction (Mortiboys et al., 2008; Xxxxxx et al., 2009; Xxx et al., 2011). As previously discussed, the PINK1-Xxxxxx complex plays a role in mitochondrial turnover, fission and fusion and transport. The mechanism underlying the PINK1 – Xxxxxx interaction is not yet fully elucidated, and whilst certain studies suggest a direct binding between the two (Xxxxx et al., 2009; Xxx et al., 2010) or that PINK1 directly phosphorylates Xxxxxx (Xxx et al., 2008; Xxxxxxxx et al., 2010; Sha et al., 2010; Xxxxx-Xxxxx et al., 2010), others suggest that they localise in separate complexes (Xxxxxx et al., 2011; Xxxxxxx et al., 2012). Recent studies also suggest that PINK1 targets Xxxxxx to the mitochondrial membrane via phosphorylation of specific substrates, such as the primary motor/adaptor complex component Miro (Xxxx et al., 2011). Specific proteosomal degradation of Miro via Xxxxxx, inhibits further mitochondrial movement and...