Reactome | DELE1(143-515) is released into the cytosol

DELE1(143-515) is released into the cytosol

Stable Identifier

R-HSA-9840401

Type

Reaction [omitted]

Species

Homo sapiens

Compartment

mitochondrial inner membrane, cytosol

ReviewStatus

5/5

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DELE1(143-515) is released into the cytosol

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In unstressed mitochondria, DELE1 is completely imported into the matrix and degraded by LONP1 (Fessler et al. 2022, Sekine et al. 2023), however during depolarization of the inner membrane (Fessler et al. 2020, Guo et al. 2020, Fessler et al. 2022) or iron deficiency (Sekine et al. 2023) the importation of DELE1 is blocked such that the N-terminal region is located in the inner membrane and the C-terminal region is located in the intermembrane space and protrudes into the cytosol (Fessler et al. 2022, Sekine et al. 2023). OMA1 located at the inner membrane cleaves the N-terminal region of DELE1 and the C-terminal cleavage product is released from the intermembrane space into the cytosol (Fessler et al. 2020, Guo et al. 2020, Fessler et al. 2022). DELE1 stalled on the surface of the outer membrane can also activate EIF2AK1 (HRI) (Sekine et al. 2023).

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
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