Reactome | Intermediate 2 binds MT-ND1:NDUFAF5:NDUFAF6 to form a 315kDa subcomplex

Intermediate 2 binds MT-ND1:NDUFAF5:NDUFAF6 to form a 315kDa subcomplex

Stable Identifier

R-HSA-6799191

Type

Reaction [binding]

Species

Homo sapiens

Compartment

mitochondrial inner membrane

ReviewStatus

5/5

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Intermediate 2 binds MT-ND1:NDUFAF5:NDUFAF6 to form a 315kDa subcomplex

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A complex I intermediate of 315kDa (reestimated from the original 400kDa) is formed centred around the core subunits NADH dehydrogenase [ubiquinone] iron-sulfur proteins 2 and 3 (NDUFS2 and NDUFS3) with other complex I subunits and assembly factor subunits (forming IP and HP subcomplexes). The IP subcomplex is anchored to the inner mitochondrial membrane by NADH-ubiquinone oxidoreductase chain 1 (MT-ND1) (together with NDUFAF5 and/or 6) (Mckenzie & Ryan 2010, Andrews et al. 2013). NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 8 (NDUFAF8) and Protein preY (PYURF, NDUFAFQ) are required for stabilization of NDUFAF5 (Floyd et al., 2016; Rensvold et al., 2022; Peker et al., 2023). Defects in NDUFAF8 cause Complex I deficiency, manifesting as Leigh syndrome (Alston et al., 2019).

Literature References

PubMed ID	Title	Journal	Year
35614220	Defining mitochondrial protein functions through deep multiomic profiling Rensvold, JW, Shishkova, E, Sverchkov, Y, Miller, IJ, Cetinkaya, A, Pyle, A, Manicki, M, Brademan, DR, Alanay, Y, Raiman, J, Jochem, A, Hutchins, PD, Peters, SR, Linke, V, Overmyer, KA, Salome, AZ, Hebert, AS, Vincent, CE, Kwiecien, NW, Rush, MJP, Westphall, MS, Craven, M, Akarsu, NA, Taylor, RW, Coon, JJ, Pagliarini, DJ	Nature	2022
27499296	Mitochondrial Protein Interaction Mapping Identifies Regulators of Respiratory Chain Function Floyd, BJ, Wilkerson, EM, Veling, MT, Minogue, CE, Xia, C, Beebe, ET, Wrobel, RL, Cho, H, Kremer, LS, Alston, CL, Gromek, KA, Dolan, BK, Ulbrich, A, Stefely, JA, Bohl, SL, Werner, KM, Jochem, A, Westphall, MS, Rensvold, JW, Taylor, RW, Prokisch, H, Kim, JP, Coon, JJ, Pagliarini, DJ	Mol Cell	2016
20552642	Assembly factors of human mitochondrial complex I and their defects in disease McKenzie, M, Ryan, MT	IUBMB Life	2010
24191001	Assembly factors for the membrane arm of human complex I Andrews, B, Carroll, J, Ding, S, Fearnley, IM, Walker, JE	Proc. Natl. Acad. Sci. U.S.A.	2013
37159021	A two-step mitochondrial import pathway couples the disulfide relay with matrix complex I biogenesis Peker, E, Weiss, K, Song, J, Zarges, C, Gerlich, S, Boehm, V, Trifunovic, A, Langer, T, Gehring, NH, Becker, T, Riemer, J	J Cell Biol	2023
31866046	Pathogenic Bi-allelic Mutations in NDUFAF8 Cause Leigh Syndrome with an Isolated Complex I Deficiency Alston, CL, Veling, MT, Heidler, J, Taylor, LS, Alaimo, JT, Sung, AY, He, L, Hopton, S, Broomfield, A, Pavaine, J, Diaz, J, Leon, E, Wolf, P, McFarland, R, Prokisch, H, Wortmann, SB, Bonnen, PE, Wittig, I, Pagliarini, DJ, Taylor, RW	Am J Hum Genet	2020