Molecular Mechanisms and Physiological Significance of Organelle Interactions and Cooperation - Volume II

Abstract

Eukaryotic cells contain distinct membrane-bound organelles, which compartmentalize cellular proteins to fulfil a variety of vital functions. In contrast to being isolated and static entities (e.g., peroxisomes, mitochondria, lipid droplets), organelles rather display dynamic changes, interact with each other, share certain proteins and show metabolic cooperation and cross talk. Despite great advances in the identification and characterization of essential components and molecular mechanisms associated with the biogenesis and function of organelles, investigating how organelles interact and are incorporated into metabolic pathways and signaling networks has become a novel focus in the field of cellular biology. Organelle cooperation requires sophisticated targeting systems, which regulate the proper distribution of shared proteins to more than one organelle. Organelle motility and membrane remodeling support organelle interaction and contact. This contact can be mediated by membrane proteins residing on different organelles, which can serve as molecular tethers to physically link opposing membranes. They can also contribute to the exchange of metabolites and ions, or act in the assembly of signaling platforms. In this regard, organelle communication events have been associated with important cellular functions such as apoptosis, antiviral defense, organelle division/biogenesis, ROS metabolism and signaling, and various metabolic pathways such as synthesis and breakdown of lipids including cholesterol.

In this Research Topic, we will focus on recent novel findings on the underlying molecular mechanisms and physiological significance of organelle interaction and cooperation with a particular focus on mitochondria, peroxisomes, endoplasmic reticulum, lysosomes and lipid droplets and their impact on the regulation of cellular homeostasis. Our understanding of how organelles physically interact and use cellular signaling systems to coordinate functional networks between each other is still far from being fully understood. Nevertheless, recent discoveries of defined membrane structures such as the mitochondria-ER associated membranes (MAM) are revealing how membrane domains enriched in specific proteins transmit signals across organelle boundaries, allowing one organelle to influence the function of another. In addition to its role as a mediator between mitochondria and the ER, contacts between the MAM and peroxisomes contribute to antiviral signaling, and specialized regions of the ER are supposed to initiate peroxisome biogenesis, whereas membrane contacts between peroxisomes, lipid droplets, lysosomes and the ER mediate lipid metabolism. A number of tethering complexes facilitating such contacts have been identified in recent years and more will likely follow in the near future. Additionally, the first human genetic disorders with mutations in tethering proteins have been reported. Despite these findings, the functional significance of most contact sites is still far from being understood and knowledge about the regulation of their formation and detachment is still scarce. Identifying the key molecular players of such specialized membrane structures is a prerequisite to understand how organelle communication is physically accomplished and will lead to the identification of new regulatory networks. Cytosolic messenger systems (e.g., kinase/phosphatase systems or redox signaling) may contribute to the general coordination of organelle communication but may also have a direct impact on the formation of tethering complexes. This Research Topic will integrate new findings from both modes of communication and will provide new perspectives for the functional significance of cross talk among organelles.