2014
DOI: 10.2174/1389202914666131210211033
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The Impact of Mitochondrial DNA and Nuclear Genes Related to Mitochondrial Functioning on the Risk of Parkinson’s Disease

Abstract: Mitochondrial dysfunction and oxidative stress are the major factors implicated in Parkinson’s disease (PD) pathogenesis. The maintenance of healthy mitochondria is a very complex process coordinated bi-genomically. Here, we review association studies on mitochondrial haplogroups and subhaplogroups, discussing the underlying molecular mechanisms. We also focus on variation in the nuclear genes (NDUFV2, PGC-1alpha, HSPA9, LRPPRC, MTIF3, POLG1, and TFAM encoding NADH dehydrogenase (ubiquinone) flavoprotein 2, pe… Show more

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Cited by 22 publications
(14 citation statements)
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References 239 publications
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“…These findings demonstrate that people harboring homoplasmic or high-level heteroplasmic mtDNA disease-associated mutations may not develop mitochondrial diseases, which suggests that the mitochondrial genetic environment may play a key role compensating for mtDNA disease-associated mutations. 44,45 The notion that mitochondrial function declines with age 1,46 is supported by our observation that the number of heteroplasmic variants and their alternative allele frequencies increase with advancing age. The exact mechanism underlying the age-related decline in mitochondrial function, however, remains unclear.…”
Section: Discussionmentioning
confidence: 70%
“…These findings demonstrate that people harboring homoplasmic or high-level heteroplasmic mtDNA disease-associated mutations may not develop mitochondrial diseases, which suggests that the mitochondrial genetic environment may play a key role compensating for mtDNA disease-associated mutations. 44,45 The notion that mitochondrial function declines with age 1,46 is supported by our observation that the number of heteroplasmic variants and their alternative allele frequencies increase with advancing age. The exact mechanism underlying the age-related decline in mitochondrial function, however, remains unclear.…”
Section: Discussionmentioning
confidence: 70%
“…The identification of a potential model of mitochondrial encephalopathies is of significance because the majority of genetically engineered animals targeted at nuclear genes involved in disease-causing mutations resulted in early postnatal or embryonic lethality, whereas most viable strains have no neuropathology, rendering the modeling of this group of diseases rather difficult (reviewed in detail in [19]). Importantly, some of these disease-causing genes with reported knockouts are under the regulation of PGC-1α, including POLG-1 [42], ANT-1 [43], and MFN1 [44] and 2 [45]. Of note, knockouts of several other genes not yet identified as subjects of disease-causing mutations are also considered as animal models of mitochondrial diseases, which include the PGC-1α-regulated genes Tfam and SOD2 [46].…”
Section: Discussionmentioning
confidence: 99%
“…42 Eventually, HSP70 levels are upregulated in the brain of sporadic PD cases and in parkin null mice but not in patients with early onset PD. 41,43,44 The disease association analysis highlighted the significant classification of proteins as linked to mitochondrial disease. Interestingly, proteins in this list included ATP carriers, such as VDAC1 and ADP/ATP translocases, and components of the mitochondrial protein synthesis machinery, such as the mitochondrial ribosomal protein S22 and the elongation factor Tu.…”
Section: Discussionmentioning
confidence: 99%