On Mar 21, 2022, researchers at Dr. Huimin Zhang’s group in Soochow University published an article entitled “Bidirectional regulation of structural damage on autophagy in the C. elegans epidermis” in Autophagy.
The epithelial tissues form the physical barriers of most of our organs and constantly face the challenges of physical injury and structural damage. However, whether and how the structural damage of the epithelial cells affects macroautophagy/autophagy cell-autonomously is still not fully understood.Although evidence suggests that multiple types of mechanical supporting structures within the epithelial cells are involved in regulating the autophagy process, these studiesare rather fragmented and were mostly performed on in vitro cultured cells.Therefore, comprehensive investigations of the autophagic response to structural damage in epithelial cells of live organisms are required to reveal the detailed regulatory mechanisms and in vivo physiological significance.In this work, Dr. Zhang’s group utilized the C. elegans epidermis as the model to address this question. The results showed that structural damage by mechanical wounding exerted proximal inhibitory effect and distant promotional effect on autophagy within the same epidermal cell. By disrupting individual mechanical supporting structures, they found that only damage of the basal extracellular matrix or the underlying muscle cells activated a distinct autophagic response in the epidermis. On the contrary, structural disruption of the epidermal cells at the apical side inhibited autophagy activation caused by different stress factors. Mechanistic studies showed that the basal promotional effect of structural damage on epidermal autophagy was mediated by a mechanotransduction pathway going through the basal hemidesmosome receptor and LET-363/MTOR, while the apical inhibitory effect was mostly carried out by activation of calcium signalling. Elevated autophagy in the epidermis played a detrimental rather than a beneficial role on cell survival against structural damage. The results obtained from these studies will not only help us better understand the pathogenesis of structural damage- and autophagy-related diseases, but also provide insight into more generic rules of autophagy regulation by the structural and mechanical properties of cells across species.
Dr. Huimin Zhang of Soochow University is the corresponding author. Dr. Rong Fu and Dr. Xiaowan Jiang are co-first authors. Ms. Yuyan Yang, Dr. Chunxia Wang, Dr. Yun Zhang and Ms. Yi Zhu are contributing authors. This work was supported by funds from the National Natural Science Foundation of China [31871384, 32170690 and 31900545], Natural Science Foundation of Jiangsu Province of China [BK20160009], Jiangsu Provincial Innovative Research Team, the Program for Changjiang Scholars and Innovative Research Team in University (PCSIRT-IRT1075) and the Priority Academic Program Development of Jiangsu Higher Education Institutions [PAPD].
Article URL:https://doi.org/10.1080/15548627.2022.2047345