Biology subjects

Guan, J.-L.

Publications and source records attributed to Guan, J.-L..

3 recordsLinked to original sources

bioRxiv2021

Selective MAP1LC3C (LC3C) autophagy requires noncanonical initiation regulators and the paralog-specific C-terminal peptide

LC3s are canonical proteins necessary for the formation of autophagosomes. We have previously established that two paralogs, LC3B and LC3C, have opposite activities in renal cancer, with LC3B playing oncogenic role and LC3C tumor suppressing role. LC3C is an evolutionary late gene, present only in higher primates and humans. Its most distinct feature is a C-terminal 20 amino acid peptide cleaved in the process of glycine 126 lipidation. Here we investigated mechanisms of LC3C selective autophagy. LC3C autophagy requires noncanonical upstream regulatory complexes that include ULK3, UVRAG, RUBCN, PIK3C2A, and a member of ESCRT, TSG101. We established that Postdivision Midbody Rings (PDMBs) implicated in cancer stem cell regulation are direct targets of LC3C autophagy. LC3C C-terminal peptide is necessary and sufficient to mediate LC3C-dependent selective degradation of PDMBs. This work establishes a new noncanonical human-specific selective autophagic program relevant to cancer stem cells.

cancer biology↗

bioRxiv2018

Quantitative Analysis of Interactive Behavior of Mitochondria and Lysosomes Using Structured Illumination Microscopy

Super-resolution optical microscopy has extended the spatial resolution of cell biology from the cellular level to the nanoscale, enabling the observation of the interactive behavior of single mitochondria and lysosomes. Quantitative parametrization of interaction between mitochondria and lysosomes under super-resolution optical microscopy, however, is currently unavailable, which has severely limited our understanding of the molecular machinery underlying mitochondrial functionality. Here, we introduce an M-value to quantitatively investigate mitochondria and lysosome contact (MLC) and mitophagy under structured illumination microscopy. We found that the M-value for an MLC is typically less than 0.4, whereas in mitophagy it ranges from 0.5 to 1.0. This system permits further investigation of the detailed molecular mechanism governing the interactive behavior of mitochondria and lysosomes.

cell biology↗

bioRxiv2018

Super-resolution tracking of mitochondrial dynamics with a third-row transition metal complex dye

Combining luminescent transition metal complex (LTMC) with super-resolution microscopy is an excellent strategy for the long-term visualization of the dynamics of subcellular structures in living cells. However, it remains unclear whether iridium(III) complexes are applicable for a particular type of super-resolution technique, structured illumination microscopy (SIM), to image subcellular structures.\n\nAs described herein, we developed an iridium(III) dye, to track mitochondrial dynamics in living cells under SIM. The dye demonstrated excellent specificity and photostability and satisfactory cell permeability. While using SIM to image mitochondria, we achieved an approximately 80-nm resolution that allowed the clear observation of the structure of mitochondrial cristae. We used the dye to monitor and quantify mitochondrial dynamics relative to lysosomes, including fusion involved in mitophagy, and newly discovered mitochondria-lysosome contact (MLC) under different conditions. MLC remained intact and fusion vanished when five receptors, p62, NDP52, OPTN, NBR1, and TAX1BP1, were knocked out, suggesting that these two processes are independence.

biophysics↗