TY  - JOUR
AU  - Meyer, Laura M
AU  - Koschade, Sebastian E
AU  - Vischedyk, Jonas B
AU  - Thoelken, Marlyn
AU  - Gubas, Andrea
AU  - Wegner, Martin
AU  - Basoglu, Marion
AU  - Knapp, Stefan
AU  - Kaulich, Manuel
AU  - Eimer, Stefan
AU  - Shaid, Shabnam
AU  - Brandts, Christian H
TI  - Deciphering the mitophagy receptor network identifies a crucial role for OPTN (optineurin) in acute myeloid leukemia.
JO  - Autophagy
VL  - 19
IS  - 11
SN  - 1554-8627
CY  - Abingdon, Oxon
PB  - Taylor & Francis
M1  - DKFZ-2023-02006
SP  - 2982 - 2996
PY  - 2023
AB  - 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
KW  - Animals
KW  - Mice
KW  - Mitophagy: genetics
KW  - Reactive Oxygen Species: metabolism
KW  - Autophagy
KW  - Leukemia, Myeloid, Acute
KW  - Ubiquitins
KW  - Ubiquitin-Protein Ligases: metabolism
KW  - AML (Other)
KW  - MN1-driven mouse model (Other)
KW  - Mitochondrial ROS (Other)
KW  - Multiplex CRISPR screen (Other)
KW  - genetic interactions (Other)
KW  - leukemia (Other)
KW  - Reactive Oxygen Species (NLM Chemicals)
KW  - Mdivi-1 (NLM Chemicals)
KW  - Ubiquitins (NLM Chemicals)
KW  - Ubiquitin-Protein Ligases (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:37439113
DO  - DOI:10.1080/15548627.2023.2230839
UR  - https://inrepo02.dkfz.de/record/284417
ER  -