Reactome | AFG3L2:SPG7 degrades SMDT1 (EMRE)

AFG3L2:SPG7 degrades SMDT1 (EMRE)

Stable Identifier

R-HSA-9839059

Type

Reaction [uncertain]

Species

Homo sapiens

Compartment

mitochondrial inner membrane

ReviewStatus

5/5

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AFG3L2 and SPG7 (Paraplegin) 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 and is processively unfolded and translocated by an ATP-dependent mechanism to enter the central pore formed by the protease domains, where it is degraded (Puchades et al. 2019). The AFG3L2:SPG7 complex binds and degrades SMDT1 (EMRE), an inner membrane localized regulatory subunit of the MCU complex, which 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 Bakka, K, König, T, Rizzuto, R, Guerrero-Castillo, S, Korwitz, A, Brandt, U, Langer, T, De Stefani, D, Tröder, SE, Lampe, PA, Rugarli, EI, Decker, T, Richter-Dennerlein, R, Lauria, I, Paggio, A, Mühlmeister, M, Patron, M	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 Casari, G, Cassina, L, Atorino, L, Silvestri, L, Marconi, R, Langer, T, Koppen, M, Ballabio, A	J Cell Biol	2003
31327635	Unique Structural Features of the Mitochondrial AAA+ Protease AFG3L2 Reveal the Molecular Basis for Activity in Health and Disease Glynn, SE, Wiseman, RL, Song, A, Lander, GC, Puchades, C, Ding, B	Mol Cell	2019
17101804	Variable and tissue-specific subunit composition of mitochondrial m-AAA protease complexes linked to hereditary spastic paraplegia Casari, G, Rugarli, EI, Metodiev, MD, Langer, T, Koppen, M	Mol Cell Biol	2007
19841671	Crystal structure of the ATPase domain of the human AAA+ protein paraplegin/SPG7 van den Berg, S, Hammarström, M, Holmberg-Schiavone, L, Schüler, H, Sagemark, J, Johansson, I, Karlberg, T	PLoS One	2009
28396416	Proteolytic control of the mitochondrial calcium uniporter complex Williams, C, Phillips, CB, Wu, Y, Miller, C, Tsai, MF, Ranaghan, M, Pao, PC, Tsai, CW	Proc Natl Acad Sci U S A	2017