OMA1 cleaves DELE1

Stable Identifier
Reaction [transition]
Homo sapiens
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OMA1 activated by depolarization of the mitochondrial inner membrane cleaves DELE1 in the N-terminal region (Fessler et al. 2020, Guo et al. 2020, Cheng et al. 2022, Fessler et al. 2022). Whereas the N-terminal region of uncleaved DELE1 is anchored in the mitochondrial inner membrane (Guo et al. 2020, Fessler et al. 2022), the C-terminal fragment of DELE1 is released into the cytosol where it activates the kinase activity of EIF2AK1 (HRI) to phosphorylate the EIF2S1 subunit of the eIF2 complex (Fessler et al. 2020, Guo et al. 2020, Cheng et al. 2022). OMA1 activity is negatively regulated by interaction with the PHB2:STOML2 complex (Cheng et al. 2022). An intermediate length processing product of DELE1 is observed in the mitochondrial matrix (Fessler et al. 2022) leading to the hypothesis that DELE1 is completely imported into the matrix and degraded by LONP1 in unstressed mitochondria (Fessler et al. 2022, Sekine et al. 2023). Upon mitochondrial stress, import of DELE1 into the matrix is blocked and OMA1 at the inner membrane cleaves the N-terminal region of DELE1 resulting in release of the C-terminal fragment into the cytosol (Fessler et al. 2022, Sekine et al. 2023). The PHB2:STOML2 complex interacts with OMA1 and inhibits cleavage of DELE1 (Cheng et al. 2022).
Literature References
PubMed ID Title Journal Year
35388015 DELE1 tracks perturbed protein import and processing in human mitochondria

Fessler, E, Jae, LT, Krumwiede, L

Nat Commun 2022
32132707 Mitochondrial stress is relayed to the cytosol by an OMA1-DELE1-HRI pathway

Unger, BA, Tian, R, Liu, Y, Xu, K, Lin, YT, Guo, X, Kampmann, M, Correia, MA, Wiita, AP, Aviles, G

Nature 2020
32132706 A pathway coordinated by DELE1 relays mitochondrial stress to the cytosol

Schmitt, S, Mancilla, IA, Fessler, E, Meyer-Bender, MF, Jae, LT, Eckl, EM, Philippou-Massier, J, Zischka, H, Krebs, S, Hanf, M

Nature 2020
35163244 The Mitochondrial PHB2/OMA1/DELE1 Pathway Cooperates with Endoplasmic Reticulum Stress to Facilitate the Response to Chemotherapeutics in Ovarian Cancer

Wang, B, Kong, Q, Sun, L, Dong, D, Yu, H, Cheng, M, Shen, L

Int J Mol Sci 2022
37327776 A mitochondrial iron-responsive pathway regulated by DELE1

Sekine, Y, Fessler, E, Houston, R, Jae, LT, Sekine, S, Narendra, DP, Eckl, EM

Mol Cell 2023
Catalyst Activity

metalloendopeptidase activity of OMA1(144-447):Zn2+ [mitochondrial inner membrane]

This event is regulated
Orthologous Events
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