Mitochondrial complex I subunit composition and assembly factors
Complex I, or NADH:ubiquinone oxidoreductase, is the first enzyme of the respiratory chain in the cristae membrane. It passes electrons from NADH to a quinol and uses the released energy to pump protons.12 Structural work describes it as a peripheral arm joined to a membrane arm, built from named subunits.4 One study concluded that binding of the assembly factor NDUFAF2 prevents ROS production from a partially assembled complex I.6
- Earliest held
- 2015, Kühlbrandt W
- Most discussed in
- Mitochondrial Structure and Bioenergetics in…, 2021
- In the library
- 41 passages in 11 works
- Rewritten
- 2026-11-01
Place in the chain
Kühlbrandt (2015) placed complex I with complexes III and IV as one of three large membrane complexes that generate the proton gradient across the cristae membrane. He described complex I as the entry point for electrons from the soluble carrier NADH, which it transfers to a quinol in the membrane.1 He added that the energy released in this transfer pumps four protons from the matrix into the crista lumen.2 Complex II, by contrast, feeds electrons to quinol without adding to the gradient.
Arms and supercomplexes
Letts and colleagues (2019) resolved complex I within a supercomplex with complex III. They found that contact between the peripheral arm and the membrane arm, through the subunits NDUFA5 and NDUFA10, appears only in the closed state. They suggested that flexibility in the peripheral arm may therefore pass into the membrane arm.4 Fedor and Hirst (2018) noted that the respirasome is generally treated as the minimal functional unit, and that it has been proposed to stabilize complex I.3
Assembly factors
Caruana and Stroud (2020) observed that complete high-resolution structures now exist for four of the five OXPHOS complexes, and that mapping mass-spectrometry data onto them helps show the roles of subunits and assembly factors.5 They described the first structure of a complex I assembly intermediate. The authors of that study found an NDUFAF2 homologue bound to an incomplete complex I from cells lacking NDUFS6. They concluded that it sits in the position later taken by NDUFA12 and blocks NDUFS6 binding.6 Protasoni and Zeviani (2021) described the ND2 module as binding assembly factors including ACAD9, ECSIT, TMEM126B, NDUFAF1 and COA1. These form the MCIA group.8
Complex I feeds electrons from the soluble carrier molecule NADH into the respiratory chain and transfers them to a quinol in the membrane.
Kühlbrandt W, 2015 · Structure and function of mitochondrial membrane protein complexes · open at passage 21The energy released in the electron transfer reaction is utilized for pumping four protons from the matrix into the crista lumen.
Kühlbrandt W, 2015 · Structure and function of mitochondrial membrane protein complexes · open at passage 21The CI1:CIII2:CIV1 “respirasome” is generally considered the minimal functional unit of the respiratory chain, and its formation has been proposed to stabilize CI through close interactions with CIII and CIV
Fedor JG, Hirst J, 2018 · Mitochondrial Supercomplexes Do Not Enhance Catalysis by Quinone Channeling · open at passage 2A major difference between the closed and open states is that contact between the CI peripheral arm and membrane arms via NDUFA5 and NDUFA10 is seen only in the closed state
Letts JA, Fiedorczuk K, Degliesposti G, Skehel M, Sazanov LA, 2019 · Structures of Respiratory Supercomplex I+III<sub>2</sub> Reveal… · open at passage 36Complete high-resolution structures now exist for four of the five OXPHOS complexes, as well as multiple variations of the respiratory chain supercomplex.
Caruana NJ, Stroud DA, 2020 · The road to the structure of the mitochondrial respiratory chain supercomplex · open at passage 4The authors conclude that assembly factor NDUFAF2 binds to the position eventually occupied by the subunit NDUFA12, preventing the binding of NDUFS6
Caruana NJ, Stroud DA, 2020 · The road to the structure of the mitochondrial respiratory chain supercomplex · open at passage 12astrocytes have less efficient mitochondrial respiration and increased ROS formation when compared to neurons, in part due to a lower incorporation of complex I into supercomplexes
Rose J, Brian C, Pappa A, Panayiotidis MI, Franco R, 2020 · Mitochondrial Metabolism in Astrocytes Regulates Brain Bioenergetics… · open at passage 41This subassembly binds to numerous assembly factors: ACAD9, ECSIT, TMEM126B, NDUFAF1, COA1 and the putative assembly factor TMEM186, which form the mitochondrial complex I intermediate assembly (MCIA)
Protasoni M, Zeviani M, 2021 · Mitochondrial Structure and Bioenergetics in Normal and Disease Conditions · open at passage 52