| Mt DNA somatic mutation | (Dolle, 2016 #1416) | In DA SN neurons of healthy individuals, mtDNA copy number increases with age, maintaining the pool of wild-type mtDNA population in spite of accumulating deletions. This upregulation fails to occur in individuals with PD, however, resulting in depletion of the wild-type mtDNA population. By contrast, neuronal mtDNA point mutational load is not increased in PD . |
Location of mitochondria
- (MacAskill, 2010 #913) in neurons, mitochondria can be found enriched at various locations with a high energy demand, including, pre- and post-synaptic domains, the axon initial segment, nodes of Ranvier and growth cones [2].
- Mitochondria are distributed ubiquitously throughout the cytoplasm of the entire nerve cell and are especially plentiful at presynaptic specializations. (https://nba.uth.tmc.edu/neuroscience/m/s1/chapter08.html)
→ js: then should be more enriched in striatum than in SN
Structure of mitochondria
- Size: 0.5 to 10 μm.
| Complex I | Complex II | Complex III | Complex IV | Complex V |
|---|---|---|---|---|
| NADH dehydrogenase | Succinate dehydrogenase | Ubiquinol cytochrome C Oxidoreductase | Cytochrome C oxidase | ATP synthase |
| 45 subunits | 4 subunits | 11 subunits | 13 subunits | 17 subunits |
| 7 mtDNA / 38 nDNA | 0 mtDNA / 4 nDNA | 1 mtDNA / 10 nDNA | 3 mtDNA / 10 nDNA | 2 mtDNA / 15 nDNA |
ETC diagram (membrane bilayer, left → right):
- Complexes I, II, III, IV, V embedded in inner membrane; H+ pumped from Matrix to Intermembrane Space; e- shuttling via Q (ubiquinone) and Cyt c
- Left-side cycles: NADH ↔ NAD+ (Citric Acid Cycle), Succinate → Fumarate (succinate · FAD → Fumarate · FADH₂, Citric Acid Cycle); Organic acid oxidation
- Complex IV: O₂ + 2H+ → H₂O (½ O₂)
- Complex V: ADP + Pi → ATP, with H+ flow back to matrix
3D mitochondrion illustration labels: DNA, ribosomes, matrix, outer membrane, inner membrane, intermembrane space, cristae · MITOCHONDRIA-STRUCTURE
| 구조물 | ||||
|---|---|---|---|---|
| Outer membrane | In yeast, about 40 MOM proteins | |||
| ERMES complex | Regulate contact to ER | |||
| Porin = integral membrane protein : | eg. VDAC | MOST Abundant | ||
| Initial import receptors | TOM70 | |||
| TOM20 | ||||
| general import pore (GIP) complex | (central receptor) Tom22, | central receptor and is associated with the channel-forming subunit Tom40. {Meisinger, 2001 #1194} represent the functional core unit that stably holds accumulated preproteins. | ||
| (channel) Tom40 | {Meisinger, 2001 #1194} represent the functional core unit that stably holds accumulated preproteins. | |||
| Tom7, (one of three small Tom proteins) | modulate assembly steps of the GIP complex ( | |||
| Tom6, (one of three small Tom proteins) | modulate assembly steps of the GIP complex ( | |||
| Tom5 (one of three small Tom proteins) | mediates transfer of preproteins from Tom22 to Tom40 (10), | |||
| intermembrane space (주름 사이) | The space between the outer and inner membranes | |||
| Inner membrane | far less permeable, allowing only very small molecules to cross into the gellike matrix |
| ||
| function | ||||
| I |
Js: electron transfer & proton translocation 이 두 process 축임.
|
In mammals, complex I consists of 45 subunits, The first electron transfer is from NADH to FMN (Flavin mononucleotide) within the mitochondrial inner membrane. This electron is then transferred to CoQ10 through Fe-S clusters. The transfer of electrons is coupled to the translocation of protons across the membrane (Schultz and Chan, 2001). MC1 이 NADH 로부터 electron (hydrogen) 을 빼앗아 ('oxidize') → electron 이 FMN 거쳐 Fe-S cluster 거쳐 → CoQ10 (=ubiquinone) 으로 전달된다 This is coupled with pumping protons (H+) from mitochondrial matrix to the intermembrane space (ie 바깥쪽으로), → which creates an electrochemical proton gradient that drives the synthesis of ATP via ATP synthase. MC1 = NADH ubiquinone oxidoreductase (= Type I NADH dehydrogenase = NADH-CoQ Reductase, 중간의 FMN 과 Fe-S cluster 생략하고 맨앞과 맨뒤를 아울러서 명명했군), It oxidizes NADH: so NADH → NAD+
| one of the main sites at which premature electron leakage to oxygen occurs, thus being one of the main sites of production of superoxide | |
| II | = succinate dehydrogenase | |||
| III | = ubiquinol-cytochrome c oxidoreductase (complex III, or cytochrome bc1 complex, Proton pump | |||
| IV | = cytochrome c oxidase, Proton pump, 여기서 oxygen 이 electron 받으며, (소모되며) water 생산함. 이것이 O2 를 소비함 (O2 에 전자 주면서) | |||
| V | = ATP synthase, uses that electrochemical gradient to synthesize ATP from ADP (cf. oligomycin, an inhibitor of complex V) | |||
|
mitochondrial permeability transition pore (mPTP or MPTP; also referred to as PTP, mTP or MTP) is a protein that is formed in the inner membrane of the mitochondria under certain pathological conditions such as traumatic brain injury and stroke. the only MPTP components identified so far are the TSPO (previously known as the peripheral benzodiazepine receptor) located in the mitochondrial outer membrane and cyclophilin-D in the mitochondrial matrix.[17][18] its Opening → increase in the permeability of the mitochondrial membranes to molecules of less than 1500 Daltons → draw water in by increasing the organelle's osmolar load.[35] → mitochondria to swell → outer membrane to rupture, → releasing cytochrome c.[35] → apoptosis (by activating pro-apoptotic factor) or necrosis NRG Tx | ||||
| matrix. | The space inside the inner membrane | Citrate synthase, a rate-limiting enzyme in the first step of TCA cycle 9, is localized in the mitochondrial matrix within eukaryotic cells, and thus can be used as a quantitative marker for the presence of intact mitochondrial mass | ||
| cristae | formed by infoldings of inner membrane | |||
| mitochondrial DNA | This DNA is small and circular. It has only 16,500 or so base pairs in it. And it encodes different proteins that are specific for the mitochondrial, - (Taanman, 1999 #937) double-stranded, circular molecule of 16,569 bp and contains 37 genes coding for two rRNAs, 22 tRNAs and 13 polypeptides. | |||
| mitochondrial network o Interaction (network, MIN) |
| |||
| 양성자: 양성자, symbol p or p+, with a positive electric charge of +1e elementary charge | ||||
Oxidoreductase:
- a- Definition
is an enzyme that catalyzes the transfer of electrons from one molecule, the reductant, also called the electron donor, to another, the oxidant, also called the electron acceptor.
- b- Function
Transmembrane oxidoreductases create electron transport chains in bacteria, chloroplasts and mitochondria, including respiratory complexes I, II and III. This group of enzymes usually utilizes NADP or NAD+ as cofactors.[1][2]
electron 을 빼앗음.
| 산화, oxidation, |
| Electron Donor (reductant) → electron Acceptor (oxidant) |
| NADH → NAD+ |
| ↓ electron |
| ↓ hydrogen |
| ↑ oxygen |
Nomenclature: donor-acceptor oxidoreductase (ie NADH-ubiquinone oxidoreductase), or donor dehydrogenase (ie NADH dehydrogenase), acceptor reductase
Electrons enter the respiratory chain at Complex I from NADH, or Complex II as it catabolizes succinate. Both Complexes transfer electrons to Coenzyme Q, which then passes the electrons to Complex III. Cytochrome c further transfers electron to Complex IV, which combines them with oxygen to produce water. All four Complexes use energy from the electron flow to pump protons from the mitochondrial matrix into the intermembrane space. The proton gradient generated in this process adds about half of its energy to the synthesis of ATP via Complex V. Thus, together, Complexes I-IV, CoQ and cytochrome c form ETC and with Complex V, ATP synthase, they form the mitochondrial respiratory chain.
Resources: https://neuromuscular.wustl.edu/pathol/diagrams/mito.htm
MITOCHONDRIAL RESPIRATORY CHAIN: COMPOSITION
| Enzyme | Reductase ✻ | Reductase ✻ | Reductase ✻ | Oxidase ✻ | |||
|---|---|---|---|---|---|---|---|
| Molecular mass | ~980 kDa | 123141.30 g/mol (=~123 kDa) https://collab.its.virginia.edu/access/content/group/f85bed6c-45d2-4b18-b868-... | {Davies, 2018 #1037} 496-kDa dimeric | {Davies, 2018 #1037} 204 kDa | {Davies, 2018 #1037, 2nd} Bovine complex IV crystallizes as a dimer | ||
Uncertain Spans
| location | transcription | uncertainty |
|---|---|---|
| ETC complexes diagram inner labels (Q, Cyt c, ½ O₂, Organic acid oxidation) | small inline diagram labels | The diagram contains many small labels (Q, Cyt c, ½ O₂, e-, H+) that are partially overlapped by membrane bilayer art; transcribed only the most legible. |
| 3D mitochondrion illustration credit/caption | ”MITOCHONDRIA-STRUCTURE” | Single bold caption visible; no smaller credit/source text legible in the crop. |
| mitochondrial network thumbnails b, c adjacency matrices | ”(0 1 1 / 1 0 0 / 1 0 0)” / “(0 1 1 / 1 0 1 / 1 1 0)“ | The 3×3 matrices in panels b and c are small and partly anti-aliased; values transcribed from the most legible reading. |
| Outer membrane → general import pore “Tom7 / Tom6 / Tom5” line ends | ”small Tom proteins” | Line is cut off at the right edge of crop r02_c01; transcribed as visible. |
| MITOCHONDRIAL RESPIRATORY CHAIN molecular mass URL | full URL | The URL “https://collab.its.virginia.edu/access/content/group/f85bed6c-45d2-4b18-b868-…” is truncated at the right edge of the page in the visible portion. |
| Inner-membrane right-most “outermost column” (column “one of the main sites…“) | placement | The right-most column with “one of the main sites at which premature electron leakage to oxygen occurs” appears narrow; column boundaries inferred. |