| 39kDa | 30kDa | 20kDa | 15kDa | 8kDa | |
|---|---|---|---|---|---|
| CTL | 2101 401 | 2034 432 | 3071 221 | 2622 170 | 2942 333 |
| PD | 2326 259 | 2290 269 | 3410 255 | 2796 196 | 1959 626 |
| P-value | 0.15 | 0.13 | 0.005 | 0.05 | 0.0004 |
Figure 2. Western blot of CTL and PD mitochondria for complex I subunits. The same mitochondrial preparations from frontal cortex samples were used for all figures. The blot images are shown for CTL and PD mitochondrial samples, and localization of the complex I subunit bands was performed as described previously (Triepels et al., 2001; Murray et al., 2003). The table at the bottom gives the actual mean band densitites with the SDs underneath. p values indicated highly significant differences for the 20 and 8 kDa subunits. See Materials and Methods for details.
xxxiv) We found no changes in levels of ETC proteins from complexes II–V xxxv) NADH-driven electron transfer rates through complex I inversely correlate with complex I protein oxidation status and positively correlate with reduction inPD8kDasubunit. xxxvi) Reduced complex I function in PD brain mitochondria appears to arise from oxidation of its catalytic subunits from internal processes, not from external oxidative stress, and correlates with complex I misassembly. (‘complex I auto-oxidation’)
(Pyle, 2016 #946) — Fig. 1 panels A (PBC, ****), B (SNpc, ***), C (FC).
Fig. 1. Analysis of mitochondrial DNA (mtDNA) content in 3 tissues, showing mean mtDNA copy number per cell (with 95% CI) for PD cases (A, shaded) and matched controls (C, unshaded) from (A) peripheral blood cells (PBC), (B) substantia nigra pars compacta (SNpc), and (C) frontal cortex (FC). Asterisks indicate statistical significance (***p = 10⁻⁴ and ****p = 10⁻³). Abbreviation: PD, Parkinson’s disease.
xxxvii) SN에서만 주네 (CSF/SERUM에서는 안 보이겠네)
| (Pyle, 2015 #2363) | ↓ mtDNA copy number in PD | |
| (Sanders, 2014 #1411) | xxxviii) ↑ Mt DNA damage: ↑ abasic sites (probed with aldehyde-reactive probe) selectively in SN dopamine neurons in PD | |
| fibroblast | (del Hoyo, 2010 #718) | (N=20 for PD) ↓ MC5 activity, MC1,2,3,4 는 모두 불변 (OR 약간증가) |
| (Mytilineou, 1994 #1360) | PD (n=6) Decreased pyruvate oxidation | |
| (Tatton, 1998 #1361) | ↓ MMP | |
| (Wiedemann, 1999 #1362) | (N=14 for PD), Flux control coefficient 로 한 것만 있으므 MC1, MC4 모두 약간 2191 | |
| (Musanti, 1993 #1363) | Cholesterol 관련만 본 듯 | |
| (Winkler-Stuck, 2004 #1040) | PD (N=18), Large interindividual difference, 오히려 ↑ MC1 activity, =MC4 activity (decreased but 통계적 유의성없어), =pyruvate | |
| (Shults, 1997 #1364) | MC1 activity 줬다는 것 같은데 결과 x | |
| Carling 2020 | N=100 Spd, n=50 control, ) =ATP, =MMP, ↓ NDUFB8 (Complex I), ↓ COX2 (mc4), = MC II/SDHB, = complex III/UQCRC2, =complex V/ATP5A | |
| (Miller, 2019 #732) 2nd | xxxix) - Significant decrease in mtDNA copy number is observed in PD patient blood cells independent of age and gender [36,92] correlating with changes ob served n postmortem brain [36,92], but see [20].- Reduced cell-free circulating mtDNA levels in the cerebrospinal fluid are detected in early-stage Parkinson's disease [92].Methylated mitochondrial DNA (mtDNA) was reported to be reduced in the CSF of PD patients, but with no association between age, gender or clinical presentation and severity | |
| Skeletal muscle | (most studies performed with isolated mitochondria). There have been reported normal activities of mitochondrial respiratory chain complexes I-IV [6-10], or decreased activities of complexes I [11-16], II [11-14] or IV [15-17]. | |
| Platelets | (most studies performed with isolated mitochondria). There have been reported normal activities [6,18-20], or decreased activities of complex I [21-26], complex II+III [25] or complex IV [24].• | |
| Lymphocytes | . Studies with homogenates showed decreased activities of complex I [23] or complexes I and IV [27], while studies with isolated mitochondria showed normal activities [28], or decreased activity of complexes I and I+III [29], and complex IV [29].• | |
| PBMC | (Smith, 2018 #1420) | =mt content (MitoTracker), ↑ mitochondrial ROS, ↓ (ANTIOXIDANT) SUPEROXIDE DISMUTASE, ↑ GLYCOLYSIS (we have shown that the glycolysis disease phenotype is not driven by monocyte activation or glucose uptake, Reduced COX4 expression may contribute to defective mitochondrial function and a propensity toward glycolysis as a preferred energy production pathway..) , = OCR, |
| monocyte | ↓ mt content (MitoTracker), ↓ ROS | |
| Leukocyte | (Müftüoglu, 2004 #1027 10 patients from 6 families with parkin gene mutations, 20 patients with sPD | ) decreased complexes I and IV activities in leukocytes from patients with idiopathic PD, and decreased complex I activity, with normality of complex IV, in patients with parkin mutations (by 62.5%) and Spd (by 64.5%): table 2, fig1 (seems clearly differentiated) |
| Spermatozoa | . Our group showed similar mitochondrial respiratory chain enzymes activities correctedby citrate synthase (CS), in the spermatozoa frumuntreated PD patients [31]. | |
| serum | (Davis, 2020 #1090)ELISA | = FGF-21, = GDF-15, and = blood mtDNA copy number (Davis, 2020 #1090) — panel A: Biomarker concentration (pg/mL) FGF-21/GDF-15 box plots for Control / PD / EOPD / LOPD with `p=0.0049` and `p=0.001`; panel B: Relative mtDNA content for Control / PD / EOPD / LOPD. {Yao, 2017 #1091} he serum GDF15 levels of the PD patients were significantly higher |
| (Pyle, 2016 #946): mtDNA | repeat panel A (PBC, ****), B (SNpc, ***), C (FC) with same Fig. 1 caption as above. ↓ in PD (N=363) |
Function
| [Glycolysis](cytoplasm) glucose→ lactate and then [LDH (cytosol or intermemb space)] pyruvate→ (2 개의) pyruvates (most pyruvate molecules enter mitochondria and are metabolized oxidatively), NADH, ATP 생성 | → [Pyruvate oxidation] Pyruvate is oxidized (combusted) 하여 acetyl CoA 와 NADH 생성 | → [Citric acid cycle=tricarboxylic acid (TCA) cycle, citric acid 가 처리되는 cycle] acetyl CoA 가 처리되어 NADH, FADH2 생성, 그리고 ATP 5 생성 |
| ↓ (위 각각의 과정마다 나오는 NADH 가 OXPHOS 로 다 들어감) [OXPHOS, oxidative phosphorylation] (mito inner membrane). Electrons from NADH (MC1 에 의해 빼앗긴 후) travel through ETC). 이러면서 MMP (pH gradient)생성 MC4 가 O2 소모 → Proton (?) 이 ATP synthase (=MC5)로 들어감 → ATP 생성 | ||
Steps of cellular respiration
(Hand-drawn pathway diagram)
- ① GLYCOLYSIS — cytosol; glucose → 2 pyruvate; + ATP, + NADH
- ② PYRUVATE OXIDATION — pyruvate → acetyl CoA; + NADH, + CO₂
- ③ CITRIC ACID CYCLE — mitochondrial matrix; + ATP, + CO₂, + NADH, + FADH₂
- ④ OXIDATIVE PHOSPHORYLATION — across inner membrane; H⁺ gradient and e⁻ transport, O₂ → H₂O, + ATP
(Textbook diagram — Cellular Respiration)
- Glycolysis — Cytoplasm; Glucose / C6 → C3 Pyruvate molecules / C3; ATP
- Transformation of pyruvate into acetyl CoA — Pyruvate + C1 → Acetyl CoA + CoA; CO₂
- Krebs cycle — Mitochondrial matrix; ATP, CO₂
- Oxidative phosphorylation — Mitochondrial inner membrane; ATP × 4 from electrons removed from glucose, pyruvate, and acetyl CoA via Redox reactions; H₂O ← 2H⁺ + O₂
Cellular Respiration: Glycolysis is the first pathway of cellular respiration that oxidizes glucose molecules. It is followed by the Krebs cycle …
Uncertain Spans
| location | transcription | uncertainty |
|---|---|---|
Complex I subunit table second-line numbers | each cell shows two stacked numbers (mean / SD); SDs (401 / 432 / 221 / 170 / 333 for CTL and 259 / 269 / 255 / 196 / 626 for PD) are preserved verbatim and rendered as <br>-separated lines. | low confidence on whether the second-line value pattern represents SD vs. n; figure caption uses mean band densitites with the SDs underneath so SD interpretation is preferred but unverified. |
xxxv) sentence | reads NADH-driven electron transfer rates through complex I inversely correlate with complex I protein oxidation status and positively correlate with reduction inPD8kDasubunit. (no space between words at the end). | source typography preserved including missing spaces. |
Multi-tissue table / Pyle 2015 #2363 cell | reads ↓ mtDNA copy number in PD; this row may be a separate column header or a continuation of the prior row. | row context truncated by photo edges. |
(Wiedemann, 1999 #1362) cell | reads (N=14 for PD), Flux control coefficient 로 한 것만 있으므 MC1, MC4 모두 약간 2191 — the trailing 2191 looks like a citation marker but is preserved verbatim as visible in the source. | low confidence on whether 2191 is a citation key or stray OCR artifact. |
Function table TCA cell trailing characters | reads acetyl CoA 가 처리되어 NADH, FADH2 생성, 그리고 ATP 5 생성 (the 5 might be a token mark rather than the number 5). | low confidence on whether 5 is intentional or OCR drift. |