Liu 2024 Cell Death Dis

Liu JC, Zhao XY, Wu ML, Shi YF, Huang ZP, Fang LP, Zhu C, Peng X, Shi ZL, Lan LJ, Ji WL, Luo L, Feng L, Zhang ZL, Xu DE, Li S, Qin ZH, Sun YY, Schachner M, Ma QH (2024) GPR50 regulates neuronal development as a mitophagy receptor. Cell Death Dis 15:591. https://doi.org/10.1038/s41419-024-06978-y

» PMID: 39143050 Open Access

Liu Ji-Chuan, Zhao Xiu-Yun, Wu Ming-Lei, Shi Yi-Fan, Huang Ze-Ping, Fang Li-Pao, Zhu Chao, Peng Xuan, Shi Zi-Ling, Lan Li-Jun, Ji Wen-Li, Luo Li, Feng Lei, Zhang Zeng-Li, Xu De-En, Li Shao, Qin Zheng-Hong, Sun Yan-Yun, Schachner Melitta, Ma Quan-Hong (2024) Cell Death Dis

Abstract: Neurons rely heavily on high mitochondrial metabolism to provide sufficient energy for proper development. However, it remains unclear how neurons maintain high oxidative phosphorylation (OXPHOS) during development. Mitophagy plays a pivotal role in maintaining mitochondrial quality and quantity. We herein describe that G protein-coupled receptor 50 (GPR50) is a novel mitophagy receptor, which harbors the LC3-interacting region (LIR) and is required in mitophagy under stress conditions. Although it does not localize in mitochondria under normal culturing conditions, GPR50 is recruited to the depolarized mitochondrial membrane upon mitophagy stress, which marks the mitochondrial portion and recruits the assembling autophagosomes, eventually facilitating the mitochondrial fragments to be engulfed by the autophagosomes. Mutations Δ502-505 and T532A attenuate GPR50-mediated mitophagy by disrupting the binding of GPR50 to LC3 and the mitochondrial recruitment of GPR50. Deficiency of GPR50 causes the accumulation of damaged mitochondria and disrupts OXPHOS, resulting in insufficient ATP production and excessive ROS generation, eventually impairing neuronal development. GPR50-deficient mice exhibit impaired social recognition, which is rescued by prenatal treatment with mitoQ, a mitochondrially antioxidant. The present study identifies GPR50 as a novel mitophagy receptor that is required to maintain mitochondrial OXPHOS in developing neurons.

• Bioblast editor: Plangger M

Labels: MiParea: Respiration, Genetic knockout;overexpression 

Organism: Mouse  Tissue;cell: Nervous system  Preparation: Homogenate 

Coupling state: ET, LEAK, OXPHOS  Pathway: N, S, CIV, NS, ROX  HRR: Oxygraph-2k 

2024-08, CN