TY  - JOUR
A1  - Rogov, Vladimir V.
A1  - Suzuki, Hironori
A1  - Marinković, Mija
A1  - Lang, Verena
A1  - Kato, Ryuichi
A1  - Kawasaki, Masato
A1  - Buljubašić, Maja
A1  - Šprung, Matilda
A1  - Rogova, Natalia
A1  - Wakatsuki, Soichi
A1  - Hamacher-Brady, Anne
A1  - Dötsch, Volker
A1  - Đikić, Ivan
A1  - Brady, Nathan
A1  - Novak, Ivana
T1  - Phosphorylation of the mitochondrial autophagy receptor Nix enhances its interaction with LC3 proteins
T2  - Scientific reports
N2  - The mitophagy receptor Nix interacts with LC3/GABARAP proteins, targeting mitochondria into autophagosomes for degradation. Here we present evidence for phosphorylation-driven regulation of the Nix:LC3B interaction. Isothermal titration calorimetry and NMR indicate a ~100 fold enhanced affinity of the serine 34/35-phosphorylated Nix LC3-interacting region (LIR) to LC3B and formation of a very rigid complex compared to the non-phosphorylated sequence. Moreover, the crystal structure of LC3B in complex with the Nix LIR peptide containing glutamic acids as phosphomimetic residues and NMR experiments revealed that LIR phosphorylation stabilizes the Nix:LC3B complex via formation of two additional hydrogen bonds between phosphorylated serines of Nix LIR and Arg11, Lys49 and Lys51 in LC3B. Substitution of Lys51 to Ala in LC3B abrogates binding of a phosphomimetic Nix mutant. Functionally, serine 34/35 phosphorylation enhances autophagosome recruitment to mitochondria in HeLa cells. Together, this study provides cellular, biochemical and biophysical evidence that phosphorylation of the LIR domain of Nix enhances mitophagy receptor engagement.
KW  - Mitophagy
KW  - Phosphorylation
Y1  - 2017
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/46797
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-467974
SN  - 2045-2322
N1  - Rights and permissions: Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
VL  - 7
IS  - 1, Art. 1131
SP  - 1
EP  - 12
PB  - Macmillan Publishers Limited, part of Springer Nature
CY  - [London]
ER  -