Research progress of membranous organelles and their subcellular structures in China

Most of the complicated processes in living cells are conducted by or related to specialized membranous organelles, which are highly dynamic. Different organelles frequently exchange contents and are connected to form a functional network which carries out critical biological processes. Organelle dysfunction may cause cell death or human diseases. Thus, understanding organelle formation and the structural characteristics and functions of specialized organelles is the basis of interpreting cellular biological processes, and will facilitate the development of disease therapies. The mechanisms underlying the formation and function of membranous organelle are hot spots in life science research. Previous studies have been based on observations of static organelles. However, a proper understanding of dynamic organelle functions requires analysis of live cells. New techniques including electron microscopy, correlative light and electron microscopy, live-cell imaging and super-resolution microscopy have been introduced to study membranous organelles. Chinese scientists have made great breakthroughs in this field and their findings have been published in high-level journals including Cell, Nature, Science, Neuron, Cell Metabolism, Nature Cell Biology, Nature Neuroscience, Journal of Cell Biology, Proceedings of the National Academy of Sciences of the United States of America, Autophagy, etc. In this review, we will summarize the progress made by Chinese scientists in understanding the dynamic regulation of cellular organelles. With respect to organelle shaping, we will summarize the mechanisms involved in determining the tubuloreticular structure of the endoplasmic reticulum, mitochondrial dynamic tubulation, autophagosome formation, autophagic lysosome reformation, lysosome tubulation, and biogenesis of the migrasome, a newly discovered organelle. With respect to organelle interactions, we will focus on those that occur in the autophagy process, for example the interactions of autophagosomes with autolysosomes, and the interactions of autophagosomes with endosomes, mitochondria, endoplasmic reticulum and lipid droplets in selective autophagy processes. We also discuss the mutual interactions between endosomes, lysosomes and the plasma membrane. These new discoveries are supported by new technologies. We will mainly review the imaging techniques developed in China, including protein labeling, genetic code expansion, and super-resolution microscopy, especially extended-resolution structured illumination imaging and correlative light and electron microscopy. Last but not least, we will highlight future opportunities and challenges, novel research directions and possible breakthroughs in membranous organelle research. These include identifying new molecules associated with intracellular membranous organelles, exploring new functions of known organelles, uncovering the mechanisms governing exchange of contents between organelles, reconstituting membranous organelles in vitro, dissecting the physiological roles of membranous organelles, and examining organelle formation and function in different pathological conditions.