Structural insights into the recognition of phosphorylated FUNDC1 by LC3B in mitophagy

@article{Lv2016StructuralII,
  title={Structural insights into the recognition of phosphorylated FUNDC1 by LC3B in mitophagy},
  author={Mengqi Lv and Chongyuan Wang and Fudong Li and Junhui Peng and Bin Wen and Qingguo Gong and Yunyu Shi and Yajun Tang},
  journal={Protein \& Cell},
  year={2016},
  volume={8},
  pages={25 - 38}
}
Mitophagy is an essential intracellular process that eliminates dysfunctional mitochondria and maintains cellular homeostasis. Mitophagy is regulated by the post-translational modification of mitophagy receptors. Fun14 domain-containing protein 1 (FUNDC1) was reported to be a new receptor for hypoxia-induced mitophagy in mammalian cells and interact with microtubule-associated protein light chain 3 beta (LC3B) through its LC3 interaction region (LIR). Moreover, the phosphorylation modification… 
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References

SHOWING 1-10 OF 49 REFERENCES
A regulatory signaling loop comprising the PGAM5 phosphatase and CK2 controls receptor-mediated mitophagy.
Mitochondrial outer-membrane protein FUNDC1 mediates hypoxia-induced mitophagy in mammalian cells
TLDR
It is reported that FUNDC1, an integral mitochondrial outer-membrane protein, is a receptor for hypoxia-induced mitophagy, and its findings offer insights into mitochondrial quality control in mammalian cells.
Modulation of Serines 17 and 24 in the LC3-interacting Region of Bnip3 Determines Pro-survival Mitophagy versus Apoptosis*
TLDR
It is demonstrated that enhancing Bnip3-Atg8 interactions via phosphorylation-mimicked LIR mutations increased mitochondrial sequestration, lysosomal delivery, and degradation, and Importantly, mitochondria were targeted by mitophagy prior to cytochrome c release, resulting in reduced cellular cytochrom c release capacity.
Receptor-mediated mitophagy in yeast and mammalian systems
TLDR
Recent advances in the understanding of the molecular mechanisms underlying the activation of receptor-mediated mitophagy and the implications of this catabolic process in health and disease are focused on.
Structural basis for phosphorylation-triggered autophagic clearance of Salmonella.
TLDR
The NMR and crystal structures of the autophagy modifier LC3B in complex with the LC3 interaction region of optineurin either phosphorylated or bearing phospho-mimicking mutations show that the negative charge induced by phosphorylation is recognized by the side chains of Arg¹¹ and Lys⁵¹ inLC3B.
Structural Basis for Sorting Mechanism of p62 in Selective Autophagy*
TLDR
In vivo analyses demonstrated that p62 mutants lacking LC3 binding ability accumulated without entrapping into autophagosomes in the cytoplasm and subsequently formed ubiquitin-positive inclusion bodies as in autophagy-deficient cells, demonstrating that the intracellular level of p62 is tightly regulated by Autophagy through the direct interaction of LC3 with p62.
Microtubule-associated Protein 1 Light Chain 3 (LC3) Interacts with Bnip3 Protein to Selectively Remove Endoplasmic Reticulum and Mitochondria via Autophagy*
TLDR
The data indicate that Bnip3 regulates the apoptotic balance as an autophagy receptor that induces removal of both mitochondria and ER and that this process significantly reduced both mitophagy and ERphagy.
p62/SQSTM1 Binds Directly to Atg8/LC3 to Facilitate Degradation of Ubiquitinated Protein Aggregates by Autophagy*
TLDR
It is demonstrated that the previously reported aggresome-like induced structures containing ubiquitinated proteins in cytosolic bodies are dependent on p62 for their formation and p62 is required both for the formation and the degradation of polyubiquitin-containing bodies by autophagy.
ULK1 translocates to mitochondria and phosphorylates FUNDC1 to regulate mitophagy
TLDR
It is shown that FUNDC1 regulates ULK1 recruitment to damaged mitochondria, where FUNDC 1 phosphorylation by ULK 1 is crucial for mitophagy.
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