Reactome | AFG3L2:SPG7 binds SMDT1 (EMRE)

AFG3L2:SPG7 binds SMDT1 (EMRE)

Stable Identifier

R-HSA-9839053

Type

Reaction [binding]

Species

Homo sapiens

Compartment

mitochondrial inner membrane

ReviewStatus

5/5

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AFG3L2 and SPG7 (Paraplegin) subunits form a heterohexameric zinc metalloprotease that is anchored in the mitochondrial inner membrane and protrudes into the mitochondrial matrix (Atorino et al. 2003, Koppen et al. 2007). Each subunit of AFG3L2 and SPG7 contains a membrane-proximal protein unfolding ATPase domain and a membrane-distal protease domain (Karlberg et al. 2009, Puchades et al. 2019). The protein substrate threads through the central pore formed by ATPase domains in a processive and ATP-dependent manner(Puchades et al. 2019). The AFG3L2:SPG7 complex binds, unfolds, and degrades SMDT1 (EMRE), a mitochondria inner membrane localized regulatory subunit of the MCU complex (MCU:MCUB:MICU1:MICU2:SMDT1) that imports calcium into the mitochondrial matrix (Konig et al. 2016, Tsai et al. 2017).

Literature References

PubMed ID	Title	Journal	Year
27642048	The m-AAA Protease Associated with Neurodegeneration Limits MCU Activity in Mitochondria König, T, Tröder, SE, Bakka, K, Korwitz, A, Richter-Dennerlein, R, Lampe, PA, Patron, M, Mühlmeister, M, Guerrero-Castillo, S, Brandt, U, Decker, T, Lauria, I, Paggio, A, Rizzuto, R, Rugarli, EI, De Stefani, D, Langer, T	Mol. Cell	2016
14623864	Loss of m-AAA protease in mitochondria causes complex I deficiency and increased sensitivity to oxidative stress in hereditary spastic paraplegia Atorino, L, Silvestri, L, Koppen, M, Cassina, L, Ballabio, A, Marconi, R, Langer, T, Casari, G	J Cell Biol	2003
31327635	Unique Structural Features of the Mitochondrial AAA+ Protease AFG3L2 Reveal the Molecular Basis for Activity in Health and Disease Puchades, C, Ding, B, Song, A, Wiseman, RL, Lander, GC, Glynn, SE	Mol Cell	2019
17101804	Variable and tissue-specific subunit composition of mitochondrial m-AAA protease complexes linked to hereditary spastic paraplegia Koppen, M, Metodiev, MD, Casari, G, Rugarli, EI, Langer, T	Mol Cell Biol	2007
19841671	Crystal structure of the ATPase domain of the human AAA+ protein paraplegin/SPG7 Karlberg, T, van den Berg, S, Hammarström, M, Sagemark, J, Johansson, I, Holmberg-Schiavone, L, Schüler, H	PLoS One	2009
28396416	Proteolytic control of the mitochondrial calcium uniporter complex Tsai, CW, Wu, Y, Pao, PC, Phillips, CB, Williams, C, Miller, C, Ranaghan, M, Tsai, MF	Proc Natl Acad Sci U S A	2017