Table 2.
mtDNA alterations in PD.
| Alteration Type | Observed Change | Analysis Method | Patient Sample | References |
|---|---|---|---|---|
| mtDNA deletion | ↓transcription/replication-associated mtDNA molecules and ↓mtDNA copy number | real-time PCR | dopaminergic neurons in the substantia nigra | [229] |
| mtDNA deletion | ↑mtDNA deletion and ↑mtDNA copy number (MT-ND1 and MT-ND4) | quantitative PCR | cholinergic neurons from the substantia nigra | [230] |
| mtDNA deletion | ↓mtDNA copy number and ↑deletion (MT-ND1 and MT-ND4) | long-range PCR and real-time PCR | neurons from the substantia nigra | [135] |
| mtDNA deletion | ↓mtDNA, ↑MT-ND1, and ↑MT-ND4 single and multiple deletions | triplex real-time PCR | single neurons from the substantia nigra | [139] |
| mtDNA deletion | ↓mtDNA copy number | real-time PCR | Venous blood | [133] |
| mtDNA deletion | ↓mtDNA (breakpoints consistently occur in regions of sequence homology) | ultradeep sequencing | dopaminergic neurons in the substantia nigra | [231] |
| mtDNA deletion | ↑mtDNAΔ4977 deletion | PCR sequencing | Striatum | [128] |
| mtDNA deletion | ↑mtDNAΔ4977 deletion | quantitative PCR | brain tissue | [130] |
| mtDNA deletion | ↑8-OHdG and ↑oxidized coenzymeQ-10 | - | CSF | [140] |
| mtDNA deletion | defective mtDNA replication/repair | - | dopaminergic neurons in the substantia nigra | [125] |
| mtDNA point mutation |
4216T>C in MT-ND1 | PCR sequencing | substantia nigra | [232] |
| mtDNA point mutation |
5460G>A in MT-ND2 | PCR sequencing | brain tissue | [226] |
| mtDNA point mutation |
4336T>C in SNP | PCR sequencing | blood | [233] |
| mtDNA point mutation |
4336A>G in MT-TQ | PCR sequencing | brain tissue | [234] |
| mtDNA point mutation |
heteroplasmic variants in genes of complex III (CYTB) and complex IV (COXI and COXII) | PCR sequencing | substantia nigra and frontal cortex | [235] |
| mtDNA point mutation |
↑mtDNA mutation level (G→T or C→A transversions) | high-fidelity PCR protocol followed by TA cloning of the PCR | neurons in the substantia nigra (early-stage PD) | [141] |
| mtDNA methylation | ↓5-methylcytosine in the D-loop region | 454 GS FLX Titanium pyrosequencer | substantia nigra | [227] |
| mtDNA methylation | methylation levels of D-Loop Region and mtDNA copy number show no significantly difference compared with control group | MS-HRM and pyrosequencing techniques; quantitative PCR | Peripheral Blood | [236] |
Abbreviations: PD, Parkinson’s disease; PCR, polymerase chain reaction; MT-ND1, a gene encoding for NADH-ubiquinone oxidoreductase chain 1, which is a core subunit of complex I; CSF, cerebrospinal fluid; EOPD, early-onset PD; LOPD, late onset PD; SNP, a polymorphism in the tRNA gln gene; D-loop, displacement-loop;8-OHdG, 8-oxo-7,8-dihydro-29-deoxyguanosine; MS-HRM, methylation-sensitive high-resolution melting.