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. 2021 Aug 3;9:686820. doi: 10.3389/fcell.2021.686820

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Copyright © 2021 Su, Guo, Huang, Feng, Tang, Zheng and Zhu.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Phytochemical activates mitophagy to treat metabolic disorders. Phytochemical activates PINK1-Parkin-dependent mitophagy and BNIP3/NIX-dependent mitophagy to treat metabolic disorders. In PINK1-Parkin-dependent mitophagy, PINK1 phosphorylates Ser65 in the ubiquitin and ubiquitin-like domain of Parkin and further facilitates its localization from the cytosol to the outer mitochondrial membrane of dysfunctional mitochondria. Moreover, Parkin can further promote the ubiquitination of MFN1, MFN2, TOM20 and VDAC, which can be identified by autophagy receptors p62 and then bind to LC3 positive autophagosomes to promote dysfunctional mitochondria to be captured by autophagosomes. Additionally, BNIP3 and NIX are easier to bind to Bcl-2 and Bcl-XL than Beclin1, which causes the release of Beclin-1 from Beclin1-Bcl-2-Bcl-XL complexes and subsequently induces mitophagy.