PITRM1 proteolyzes mitochondrial targeting peptides (presequences)

Stable Identifier
Reaction [omitted]
Homo sapiens
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After MPP cleaves off targeting peptides (also called presequences) of proteins imported into the mitochondrial matrix, PITRM1 (also called PreP) proteolyzes the cleaved targeting peptides (Pinho et al. 2010, Alikhani et al. 2011, Teixeira et al. 2012). PITRM1 also cleaves amyloid beta peptide that is imported into the matrix (Falkevall et al. 2006). Missense mutations in PITRM1 are associated with a neurological syndrome comprising mental retardation, spinocerebellar ataxia, cognitive decline, psychosis and possible epilepsy (Brunetti et al. 2016).

Literature References
PubMed ID Title Journal Year
16849325 Degradation of the amyloid beta-protein by the novel mitochondrial peptidasome, PreP

Tjernberg, L, Eneqvist, T, Falkevall, A, Glaser, E, Johnson, KA, Pavlov, PF, Alikhani, N, Ankarcrona, M, Busch, K, Bhushan, S

J. Biol. Chem. 2006
23041349 In vitro oxidative inactivation of human presequence protease (hPreP)

Glaser, E, Levine, RL, Branca, RM, Lehtiö, J, Pinho, CM, Teixeira, PF

Free Radic. Biol. Med. 2012
21750375 Decreased proteolytic activity of the mitochondrial amyloid-β degrading enzyme, PreP peptidasome, in Alzheimer's disease brain mitochondria

Glaser, E, Du, H, Yan, SS, Alikhani, N, Pinho, CM, Yan, S, Guo, L, Chen, JX

J. Alzheimers Dis. 2011
26697887 Defective PITRM1 mitochondrial peptidase is associated with Aβ amyloidotic neurodegeneration

Brunetti, D, Johansson, S, Teixeira, P, Dallabona, C, Cerutti, R, Sztromwasser, P, Zeviani, M, Telstad, W, Ferrero, I, Glaser, E, Preziuso, C, Reyes, A, Bindoff, LA, Boman, H, D'Amati, G, Goffrini, P, Baruffini, E, Viscomi, C, Knappskog, PM, Fernandez-Vizarra, E, Torsvik, J

EMBO Mol Med 2016
19962426 Genetic and biochemical studies of SNPs of the mitochondrial A beta-degrading protease, hPreP

Eneqvist, T, Bäckman, HG, Glaser, E, Graff, C, Fratiglioni, L, Alikhani, N, Pinho, CM, Björk, BF

Neurosci. Lett. 2010
Catalyst Activity

metallopeptidase activity of PITRM1 [mitochondrial matrix]

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