Mitochondrial Respiratory Complexes (I-V)
| HASS (sub)unit | Complex I | Complex II | Complex III | Complex IV | Complex V (ATPase) |
|---|---|---|---|---|---|
| Subunit count | 45, 이중 14 central subunits (Wirth, 2016 #1038, this shows each subunits) & 30 accessory subunits surrounding the central subunits that are not directly associated with energy conservation. | (monomer 라는 듯) (1, 16, 17), but is likely to occur both as a monomer and a dimer in the membrane (18, 19). | ~14 subunits | ||
| Inhibitor | Rotenone, Amytal | TTFA, malonate | Antimycin A | Cyanide, Carbon Monoxide, Azide, Cytochrome oxidase | Oligomycin |
| Nuclear DNA Subunits | 39 | 4 | 10 | ~14 (IXE, IIA, IIIK) | |
| Mitochondrial DNA Subunits | 7 (ND1-6, ND4L) | 0 | 1 (Cytochrome b) | 3 | 2 (ATPase 6, ATPase 8) |
| Flavoprotein | Flavin mononucleotide | FAD (SDHA) | |||
| Iron protein | Iron Sulfur (FeS) protein NDUFS1 | FeS protein SDHB | Rieske FeS, Cytochrome (Heme) b, c1 | ||
| Other features | Membrane proteins Cytochrome b560 SDHC, SDHD | (Heme) a, a3, Copper protein | |||
| Disorders | Alpers / Alzheimer's / Parkinsonism / Cardiomyopathy / Deficiency / Barth / Lethal Infantile Encephalopathy / Infantile CNS / Leber's / Leigh / Longevity / MELAS / MERRF / Myopathy + CNS / PEO / Spinal cord / Kearns-Sayre | Fatal infantile / GRACILE / +CNS / Alper's / Ataxia / Deafness / Fatal / Benign Adult Rhabdomyolysis / Paraganglioma / Pheochromocytoma | PEO / KSS / MNGIE / MERRF / MELAS / Cardiomyopathy / Encephalopathy / Leigh / Multisystem / NARP | Leigh / Myopathy / Infantile + CNS |
Rotenone-binding site / Common MC1 inhibitors (pesticides)-binding sites / The catalytic core sites of MC1
| Bos Taurus (Corresponding Human genes) | ||
|---|---|---|
| Rotenone-binding site | PSST (NDUFS7) | |
| Common MC1 inhibitors (pesticides)-binding sites | PSST (NDUFS7), 49 kDa (NDUFS2) | 14 개라 함 |
| The catalytic core sites of MC1 | PSST (NDUFS7), 49 kDa (NDUFS2), TYKY (NDUFS8), ND1 (NU1M), ND5 (NU5M), ND3 (NU3M), ND6 (NU6M), ND4L (NULM), ND2 (NU2M), ND4 (NU4M), 30 kDa (NDUFS3), 75 kDa (NDUFS1), 51 kDa (NDUFV1), 24 kDa (NDUFV2) |
Rotenone
a- rotenone
rotenone binds to the PSST subunit (Of) In Yarrowia lipolytica (an yeast)) (2016 Wirth, Hirst; human?) which is a key subunit for electron transfer from the Fe-S cluster to quinone, and in the interface between the hydrophilic and hydrophobic domains of MC-I (Darrouzet et al., 1998; Schuler et al., 1999).
Rotenone inhibits 20 kDa subunit of complex I (PSST) labeling without effect on 36 kDa subunit of complex I (ND1) (Schuler, 2001 #1230, in vitro using beef heart-derived mito particle).
b- ubiquinone reduction site
A wide variety of CI (=mc1) inhibitors share a common binding domain at or close to the ubiquinone reduction site (Ino et al., 2003).
ubiquinone reduction site is formed by the 49-kDa and PSST subunits (2016 Wirth),
position: quinone reduction site ~30 Å above the membrane domain - 그 near the inner membrane이긴 한데 Peripheral arm 으로 분류됨.
Conformational changes at the ubiquinone-binding site drive proton pumping
binding to the ubiquinone binding site of CI (이건 여러 문헌에 나옴. 이것이 ubiquinone reduction site 와 같은 듯.)
(Degli Esposti, 1998 #1163) MC1 inhibitors = 0: rotenone is a type B inhibitor. type B inhibitors displace the partially reduced ubisemiquinone intermediate;
. Schematic representation of CI and proposed inhibition binding sites by inhibitors of class A, B and C. Nicotinamide adenine dinucleotide (NADH, reduced and NAD, oxidized), flavin mononucleotide (FMN) and Ubiquinone (Q) (taken from Haefeli, 2012).
a. hydrophobic inhibitors like rotenone or Piericidin A most likely disrupt the electron transfer between the terminal Fe-S cluster N2 and ubiquinone (Fig. 3A) (based on Lummen, 1998).
L-shaped MC1: peripheral arm (위 그림에서 튀어나온 것) & membrane arm
대체로 그럼 NADH쪽이 아니라 CoQ10쪽임!
(2016 Wirth에서는 human에서는 PSST subunit이 없음, so human에서의 rotenone이 정확이 어느 site에 붙는지 불명인듯함),
Fig 5. Redox-linked proton translocation by complex I
Electrons are transferred from the NADH oxidation site to the ubiquinone reduction site via a chain of iron-sulfur clusters; selected critical residues of the ubiquinone reduction site are shown in green (Tyr144, His95, His91). The membrane arm comprises three antiporter type subunits with discontinuous helices (ND5, marine; ND4, cyan; ND2, pink) corresponding to three potential proton translocation sites (black arrows). In the proximal part of the membrane arm (Pp module) the n-bulge helix of ND6 (orange) and the discontinuous helix of ND1 (red) are highlighted. Residues constituting a forth putative proton pathway (dashed arrow) are found in subunits ND2 and ND4L. In the center of the membrane arm a series of protonable residues (basic, blue; acidic, red) extends from subunit ND5 to subunit ND1 and terminates below the ubiquinone reduction site with a loop comprising a cluster of highly conserved acidic residues. Conformational changes linked to the redox chemistry of ubiquinone are proposed to induce an electric pulse that ultimately triggers proton translocation events in the membrane arm.
Rotenone structure / Complex I schematic
Complex I = NADH ubiquinone oxidoreductase. Schematic shows: Matrix side (NADH + H+ → NAD+ + H+; FMN; (FeS); CoQ; CoQH2; FeS/N2 → PSST → Rotenone Site of inhibition) / IMS side. (based on Lummen, 1998).
Uncertain Spans
| location | transcription | uncertainty |
|---|---|---|
| Source URL | 6a2353586804/2/Ch20 Lawson N Respiratory Complex I (Mitochondrial) | The source URL is partly visible at the very top of the photo and partially cut; reading is best-effort. |
| Complex II Subunits | 1 16, 17 and 18, 19 references | Reference numerals are partly obscured by the column boundary; preserved as visible. |
| Disorders cell formatting | row contains many disease names per complex | The cell separators within the disorders row are not always visible in the photo; reconstruction groups names per complex column. |
| Rotenone schematic | annotation Site of inhibition in complex I of mitochondria | Caption text is small at the bottom of the figure; reading preserved as visible. |