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

Stable Identifier
Reaction [binding]
Homo sapiens
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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

Peters, SR, Vincent, CE, Taylor, RW, Linke, V, Raiman, J, Sverchkov, Y, Hebert, AS, Brademan, DR, Shishkova, E, Cetinkaya, A, Akarsu, NA, Craven, M, Alanay, Y, Pagliarini, DJ, Pyle, A, Westphall, MS, Rush, MJP, Jochem, A, Coon, JJ, Rensvold, JW, Hutchins, PD, Salome, AZ, Miller, IJ, Manicki, M, Kwiecien, NW, Overmyer, KA

Nature 2022
27499296 Mitochondrial Protein Interaction Mapping Identifies Regulators of Respiratory Chain Function

Stefely, JA, Taylor, RW, Dolan, BK, Westphall, MS, Wilkerson, EM, Veling, MT, Wrobel, RL, Kim, JP, Jochem, A, Cho, H, Coon, JJ, Xia, C, Ulbrich, A, Gromek, KA, Rensvold, JW, Bohl, SL, Beebe, ET, Pagliarini, DJ, Werner, KM, Alston, CL, Floyd, BJ, Prokisch, H, Kremer, LS, Minogue, CE

Mol Cell 2016
20552642 Assembly factors of human mitochondrial complex I and their defects in disease

Ryan, MT, McKenzie, M

IUBMB Life 2010
24191001 Assembly factors for the membrane arm of human complex I

Fearnley, IM, Carroll, J, Andrews, B, Walker, JE, Ding, S

Proc. Natl. Acad. Sci. U.S.A. 2013
37159021 A two-step mitochondrial import pathway couples the disulfide relay with matrix complex I biogenesis

Gehring, NH, Peker, E, Becker, T, Weiss, K, Song, J, Boehm, V, Trifunovic, A, Riemer, J, Zarges, C, Langer, T, Gerlich, S

J Cell Biol 2023
31866046 Pathogenic Bi-allelic Mutations in NDUFAF8 Cause Leigh Syndrome with an Isolated Complex I Deficiency

Hopton, S, Heidler, J, Taylor, RW, Broomfield, A, Pavaine, J, Veling, MT, He, L, Diaz, J, Leon, E, Bonnen, PE, Wortmann, SB, Pagliarini, DJ, Wittig, I, Alston, CL, McFarland, R, Taylor, LS, Sung, AY, Wolf, P, Prokisch, H, Alaimo, JT

Am J Hum Genet 2020
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