Reactome | LONP1 binds mitochondrial matrix proteins

LONP1 binds mitochondrial matrix proteins

Stable Identifier

R-HSA-9838093

Type

Reaction [binding]

Species

Homo sapiens

Compartment

mitochondrial matrix

ReviewStatus

5/5

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LONP1 binds mitochondrial matrix proteins

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LONP1 binds substrate proteins and degrades them using an ATP-dependent mechanism (Mohammed et al. 2022). The binding of proteins to LONP1 can allosterically stimulate its ATPase activity (inferred from bacterial Lon proteases in Waxman et al. 1986, Lin et al. 2016). Human LONP1 binds, unfolds, and degrades several mitochondrial matrix proteins (Lee et al. 2021), including oxidized aconitase in which hydrophobic regions are exposed (Bota and Davies 2002). However, LONP1 is unable to degrade aggregated oxidized aconitase (Bota and Davies 2002). Steroidogenic acute regulatory protein (STAR) is directed to the mitochondrial matrix for degradation by LONP1 and other proteases (Ondrovicova et al. 2005, Granot et al. 2007). The mitochondrial large ribosome subunit MRPL32 is degraded by LONP1 when MRPL32 is not incorporated in the ribosome and hence not bound to nucleic acid (Kunova et al. 2017). Other ribosomal subunits appear to be similarly degraded (Kunova et al. 2017). The helicase TWNK (Twinkle, PEO1) is degraded by LONP1 regardless of its association with nucleic acid (Kunova et al. 2017). Other substrates of LONP1 may include SSBP1, MTERFD3, FASTKD2, and CLPX (Rendón and Shoubridge 2018).

Literature References

PubMed ID	Title	Journal	Year
36629048	LONP1 targets HMGCS2 to protect mitochondrial function and attenuate chronic kidney disease Wu, M, Wang, T, Jiang, M, Zhang, A, Zhang, Y, He, J, Yu, X, Xu, S, Li, Y, Wang, L, Jia, Z, Miao, M, Yang, L, Deng, X, Fan, J, Huang, S, Bai, M	EMBO Mol Med	2023
28377575	The role of Lon-mediated proteolysis in the dynamics of mitochondrial nucleic acid-protein complexes Kutejova, E, Kotrasová, V, Ambro, Ľ, Pevala, V, Bauer, JA, Bellová, J, Martináková, L, Ondrovičová, G, Kunová, N	Sci Rep	2017
12198491	Lon protease preferentially degrades oxidized mitochondrial aconitase by an ATP-stimulated mechanism Bota, DA, Davies, KJ	Nat Cell Biol	2002
33637676	LONP1 and ClpP cooperatively regulate mitochondrial proteostasis for cancer cell survival Rhee, HW, Park, DH, Chae, YC, Seo, JK, Lee, YJ, Lee, YG, Shin, KJ, Nam, Y, Kim, HW	Oncogenesis	2021
23201127	Phosphorylation of human TFAM in mitochondria impairs DNA binding and promotes degradation by the AAA+ Lon protease Temiakov, D, Bogenhagen, DF, Li, M, Nie, X, Venkatesh, S, Morozov, YI, Suzuki, CK, Lee, J, Lu, B	Mol Cell	2013
15870080	Cleavage site selection within a folded substrate by the ATP-dependent lon protease Janata, J, Perecko, D, Gakh, O, Kutejova, E, Orly, J, Li, H, Singh, K, Tian, B, Liu, T, Suzuki, CK, Ondrovicová, G, Granot, Z	J Biol Chem	2005
17579211	Turnover of mitochondrial steroidogenic acute regulatory (StAR) protein by Lon protease: the unexpected effect of proteasome inhibitors Orly, J, Oppenheim, AB, Maurizi, MR, Eimerl, S, Suzuki, CK, Lu, B, Braun, S, Granot, Z, Bahat, A, Melamed-Book, N, Kobiler, O	Mol Endocrinol	2007
35870450	Catalytic cycling of human mitochondrial Lon protease Abrahams, JP, Maier, T, Balasopoulos, D, Mohammed, I, Schmitz, KA, Schenck, N, Topitsch, A	Structure	2022