%0 Journal Article
%A Meyer, Laura M
%A Koschade, Sebastian E
%A Vischedyk, Jonas B
%A Thoelken, Marlyn
%A Gubas, Andrea
%A Wegner, Martin
%A Basoglu, Marion
%A Knapp, Stefan
%A Kaulich, Manuel
%A Eimer, Stefan
%A Shaid, Shabnam
%A Brandts, Christian H
%T Deciphering the mitophagy receptor network identifies a crucial role for OPTN (optineurin) in acute myeloid leukemia.
%J Autophagy
%V 19
%N 11
%@ 1554-8627
%C Abingdon, Oxon
%I Taylor & Francis
%M DKFZ-2023-02006
%P 2982 - 2996
%D 2023
%X The selective autophagic degradation of mitochondria via mitophagy is essential for preserving mitochondrial homeostasis and, thereby, disease maintenance and progression in acute myeloid leukemia (AML). Mitophagy is orchestrated by a variety of mitophagy receptors whose interplay is not well understood. Here, we established a pairwise multiplexed CRISPR screen targeting mitophagy receptors to elucidate redundancies and gain a deeper understanding of the functional interactome governing mitophagy in AML. We identified OPTN (optineurin) as sole non-redundant mitophagy receptor and characterized its unique role in AML. Knockdown and overexpression experiments demonstrated that OPTN expression is rate-limiting for AML cell proliferation. In a MN1-driven murine transplantation model, loss of OPTN prolonged overall median survival by 7 days (+21
%K Animals
%K Mice
%K Mitophagy: genetics
%K Reactive Oxygen Species: metabolism
%K Autophagy
%K Leukemia, Myeloid, Acute
%K Ubiquitins
%K Ubiquitin-Protein Ligases: metabolism
%K AML (Other)
%K MN1-driven mouse model (Other)
%K Mitochondrial ROS (Other)
%K Multiplex CRISPR screen (Other)
%K genetic interactions (Other)
%K leukemia (Other)
%K Reactive Oxygen Species (NLM Chemicals)
%K Mdivi-1 (NLM Chemicals)
%K Ubiquitins (NLM Chemicals)
%K Ubiquitin-Protein Ligases (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:37439113
%R 10.1080/15548627.2023.2230839
%U https://inrepo02.dkfz.de/record/284417