Mitochondrial quality control is essential for cellular homeostasis and accumulating evidence show that mitochondria can be selectively targeted for autophagic degradation (mitophagy). Mitophagy allows for the removal of dysfunctional mitochondria, which is highly implicated in energetically demanding cells including muscle and nerve cells. However, despite the well characterization of PINK1/Parkin route of mitophagy, mechanisms concerning PINK1/Parkin‐independent mitophagy are still poorly understood. With imaging approaches including structure‐illumination microscopy (SR‐SIM), here we demonstrate that the autophagy protein Syntaxin 17 (STX17), initiates mitophagy upon the depletion of outer mitochondrial membrane protein Fis1. Using mass spectrometry analysis, we identify STX17 interacts with Fis1, which preferentially gatekeeps the dynamic shuffling of STX17 between ER and mitochondria. Loss of Fis1 results in the accumulation of STX17 on mitochondria and mitochondria associated membranes (MAM), exposing its N‐terminus to assemble and self‐oligomerize for mitophagy. Mitochondrial STX17 interacts with ATG14 and further recruits core autophagy proteins hierarchically to form mitophagosomes, followed by Rab7‐dependent mitophagosome‐lysosome fusion. In addition, our results reveal that Fis1 loss impairs mitochondrial metabolic function, and potentially sensitizes mitochondria to STX17‐mediated mitochondrial engulfment within autophagosomes, which is directly initiated through canonical autophagy machinery, closely linking non‐selective macroautophagy and mitochondria. Our findings uncover a novel PINK1/Parkin‐independent mitophagy mechanism, in which outer mitochondrial membrane protein Fis1 gates the elimination of mitochondria. Support or Funding Information This work is financially supported by grants Tier 2 MOE and NUS, Singapore to Y.‐C.L. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Root gravitropism allows plants to establish root systems and its regulation depends on polar auxin transport mediated by PIN-FORMED (PIN) auxin transporters. PINOID (PID) and PROTEIN PHOSPHATASE 2A (PP2A) act antagonistically on reversible phosphorylation of PINs. This regulates polar PIN distribution and auxin transport. Here we show that a peptidyl-prolyl cis/trans isomerase Pin1At regulates root gravitropism. Downregulation of Pin1At suppresses root agravitropic phenotypes of pp2aa and 35S:PID, while overexpression of Pin1At affects root gravitropic responses and enhances the pp2aa agravitropic phenotype. Pin1At also affects auxin transport and polar localization of PIN1 in stele cells, which is mediated by PID and PP2A. Furthermore, Pin1At catalyses the conformational change of the phosphorylated Ser/Thr-Pro motifs of PIN1. Thus, Pin1At mediates the conformational dynamics of PIN1 and affects PID- and PP2A-mediated regulation of PIN1 polar localization, which correlates with the regulation of root gravitropism.

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Brominated flame retardants (BFRs) such as polybrominated diphenyl ethers (PBDEs) are important pollutants, yet few data on ambient BFRs levels have been available for North China, one of the most developed regions of the country. In this study, we investigated levels and spatial distributions of BFRs based on gridded field observations coupled with passive air sampling in the aforementioned region. A model incorporating both point and nonpoint sources was developed to simulate the spatial distribution and to achieve source apportionment. Although high concentration was observed at an electronic-waste (e-waste) recycling site, the median level of the sum of tri-, tetra-, hepta-, hexa-, and hepta-PBDEs (∑10PBDEs) was 0.56 ng/sample, which was lower than those observed previously in mainland China. Source apportionment revealed that nonpoint emissions contributed nearly 78% of ∑10PBDEs observed in this study. In contrast, high levels of BDE-209 and DBDPE were observed, with median concentrations of 4.0 and 10.2 ng/sample, respectively. Point sources located in the region around Laizhou Bay, Shandong Province were the major sources, which contributed 31% of BDE-209 and 70% of DBDPE observed in this study, indicating that this manufacturing base was the most important source region for atmospheric deca-BFRs in North China. To our knowledge, this is the first study to report source apportionment of atmospheric BFRs based on gridded field observations.

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The cis-trans peptidylprolyl isomerase Pin1 plays a critical role in regulating a subset of phosphoproteins by catalyzing conformational changes on the phosphorylated Ser/Thr-Pro motifs. The phosphorylation-directed ubiquitination is one of the major mechanisms to regulate the abundance of p27 Kip1 . In this study, we demonstrate that Pin1 catalyzes the cis-trans conformational changes of p27Kip1 and further mediates its stability through the polyubiquitination mechanism. Our results show that the phosphorylated Thr-187-Pro motif in p27Kip1 is a key Pin1-binding site. In addition, NMR analyses show that this phosphorylated Thr-187-Pro site undergoes conformational change catalyzed by Pin1. Moreover, in Pin1 knock-out mouse embryonic fibroblasts, p27Kip1 has a shorter lifetime and displays a higher degree of polyubiquitination than in Pin1 wildtype mouse embryonic fibroblasts, suggesting that Pin1 plays a critical role in regulating p27Kip1 degradation. Additionally, Pin1 dramatically reduces the interaction between p27Kip1 and Cks1, possibly via isomerizing the cis-trans conformation of p27 Kip1 . Our study thus reveals a novel regulatory mechanism for p27 Kip1 stability and sheds new light on the biological function of Pin1 as a general regulator of protein stability.

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