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Comment
. 2017 Sep 19:10:297.
doi: 10.3389/fnmol.2017.00297. eCollection 2017.

Commentary: Nix restores mitophagy and mitochondrial function to protect against PINK1/Parkin-related Parkinson's disease

Jin-Sung Park  1   2 , Brianada Koentjoro  1   2 , Carolyn M Sue  1   2
Affiliations
Comment

Commentary: Nix restores mitophagy and mitochondrial function to protect against PINK1/Parkin-related Parkinson's disease

Jin-Sung Park et al. Front Mol Neurosci. .
No abstract available

Keywords: PINK1; Parkin; Parkinson's disease; mitophagy; nix.

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Figures

Figure 1
Figure 1
Defective mitophagy in PINK1/Parkin-related Parkinson's disease and the compensatory role of Nix in restoring mitophagy. (A) In healthy mitochondria, PINK1 is cleaved by presenilin-associated rhomboid-like protease (PARL). Dissipation of mitochondrial membrane potential decreases due to damage or aging, stabilizes PINK1 on the outer mitochondrial membrane (OMM) which in turn recruits Parkin to dysfunctional mitochondria. Parkin, activated by PINK1-mediated phosphorylation, ubiquitinates OMM such as mitofusins (MFN) to which the autophagosomal receptor microtubule-associated protein 1 light chain 3 (LC3)/gamma-aminobutyric acid receptor-associated protein (GABARAP) binds with polyubiquitine-binding proteins such as p62, optineurin and nuclear dot protein 52 kDa, leading to engulfment of dysfunctional mitochondria into autophagosomes. In the presence of Parkin, NIP3-like protein X (Nix) facilitates mitophagy by Parkin-mediated ubiquitination and recruitment of the polyubiquitine-binding protein neighbor of BRCA1 (NBR1). Although, Nix may mediate mitophagy independently of Parkin, its contribution is likely minor. Degradation of engulfed mitochondria occurs by fusion of autophagosomes with lysosomes. (B) In Parkin deficiency, accumulation of PINK1 occurs on the OMM of dysfunctional mitochondria, but the downstream events of polyubiquitination and subsequent recruitment of adaptor proteins fail to take place. (C) PINK1 deficiency, on the contrary, leads to failure in recognizing dysfunctional mitochondria, severely curtailing the efficiency of mitophagy. In both conditions, dysfunctional mitochondria accumulate due to impairment in inducing mitophagy. (D) Upregulation of Nix in PINK1 or Parkin deficiency, increases presence of Nix in dysfunctional mitochondria and mediates mitophagy by forming a complex with LC3/GABARAP and ras homolog enriched in brain protein (Rheb), maintaining mitochondrial quality control system and function.
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References

    1. Bhujabal Z., Birgisdottir A. B., Sjottem E., Brenne H. B., Overvatn A., Habisov S., et al. . (2017). FKBP8 recruits LC3A to mediate Parkin-independent mitophagy. EMBO Rep. 18, 947–961. 10.15252/embr.201643147 - DOI - PMC - PubMed
    1. Chung K. K., Thomas B., Li X., Pletnikova O., Troncoso J. C., Marsh L., et al. . (2004). S-nitrosylation of Parkin regulates ubiquitination and compromises Parkin's protective function. Science 304, 1328–1331. 10.1126/science.1093891 - DOI - PubMed
    1. Dauer W., Przedborski S. (2003). Parkinson's Disease: mechanisms and models. Neuron 39, 889–909. 10.1016/S0896-6273(03)00568-3 - DOI - PubMed
    1. Fu M., St-Pierre P., Shankar J., Wang P. T., Joshi B., Nabi I. R. (2013). Regulation of mitophagy by the Gp78 E3 ubiquitin ligase. Mol. Biol. Cell 24, 1153–1162. 10.1091/mbc.E12-08-0607 - DOI - PMC - PubMed
    1. Gao F., Chen D., Si J., Hu Q., Qin Z., Fang M., et al. . (2015). The mitochondrial protein BNIP3L is the substrate of PARK2 and mediates mitophagy in PINK1/PARK2 pathway. Hum. Mol. Genet. 24, 2528–2538. 10.1093/hmg/ddv017 - DOI - PubMed

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