Organelle Membrane Extensions in Mammalian Cells

SIMPLE SUMMARY: Within cells, there are numerous compartments called ‘organelles’ that perform a range of specialised functions required to support life. Organelles are constantly adapting to their environment, changing shape and cooperating with each other depending on the cellular needs, which is essential for cell health as defects in these processes lead to human diseases. One example of organelle dynamic behaviour is the formation of thin tubules that extend and retract from the membranes that delimit the organelles. With a focus on two organelles (peroxisomes and mitochondria) that have roles in cell metabolism and protection, we examine how and why these membrane extensions form, and what their function is within the cell. This includes forming new organelles or organelle networks; increasing the organelle surface area to maximise uptake of molecules; mediating communication between different organelles. We propose that these membrane extensions allow organelles to ‘reach out’ and explore their surroundings more efficiently. Together, this review highlights the importance of organelle dynamics, and specifically membrane extension, in maintaining healthy cell function, as well as exploring the questions remaining to be answered to further our understanding of this essential aspect of cell biology. ABSTRACT: Organelles within eukaryotic cells are not isolated static compartments, instead being morphologically diverse and highly dynamic in order to respond to cellular needs and carry out their diverse and cooperative functions. One phenomenon exemplifying this plasticity, and increasingly gaining attention, is the extension and retraction of thin tubules from organelle membranes. While these protrusions have been observed in morphological studies for decades, their formation, properties and functions are only beginning to be understood. In this review, we provide an overview of what is known and still to be discovered about organelle membrane protrusions in mammalian cells, focusing on the best-characterised examples of these membrane extensions arising from peroxisomes (ubiquitous organelles involved in lipid metabolism and reactive oxygen species homeostasis) and mitochondria. We summarise the current knowledge on the diversity of peroxisomal/mitochondrial membrane extensions, as well as the molecular mechanisms by which they extend and retract, necessitating dynamic membrane remodelling, pulling forces and lipid flow. We also propose broad cellular functions for these membrane extensions in inter-organelle communication, organelle biogenesis, metabolism and protection, and finally present a mathematical model that suggests that extending protrusions is the most efficient way for an organelle to explore its surroundings.