Lights up on organelles: Optogenetic tools to control subcellular structure and organization

Abstract

Since the neurobiological inception of optogenetics, light-controlled molecular perturbations have been applied in many scientific disciplines to both manipulate and observe cellular function. Proteins exhibiting light-sensitive conformational changes provide researchers with avenues for spatiotemporal control over the cellular environment and serve as valuable alternatives to chemically inducible systems. Optogenetic approaches have been developed to target proteins to specific subcellular compartments, allowing for the manipulation of nuclear translocation and plasma membrane morphology. Additionally, these tools have been harnessed for molecular interrogation of organelle function, location, and dynamics. Optogenetic approaches offer novel ways to answer fundamental biological questions and to improve the efficiency of bioengineered cell factories by controlling the assembly of synthetic organelles. This review first provides a summary of available optogenetic systems with an emphasis on their organelle-specific utility. It then explores the strategies employed for organelle targeting and concludes by discussing our perspective on the future of optogenetics to control subcellular structure and organization.

Defunctionalizing intracellular organelles such as mitochondria and peroxisomes with engineered phospholipase A/acyltransferases

“…To test if the PLAAT strategy can be generalized to other membranebound organelles, we chose peroxisomes, since unlike mitochondria there is only a limited number of techniques available for perturbation of peroxisome functions 36 . To direct 18TM to the cytosolic surface of peroxisomes, we used peroxisomal membrane protein PEX3 37 .…”

Optogenetic Approaches for the Spatiotemporal Control of Signal Transduction Pathways

“…A possible application for the high spatial control of optogenetics is the targeting of subcellular compartments of the cell. For an in-depth review of optogenetic control of cell dynamics and subcellular applications see the recently published reviews [ 91 , 92 ], An example is the optogenetic TULIP system based on the LOV2-domain that was applied for local activation and recruitment of the RhoA GTPase to the membrane in epithelial cells ( Figure 6 A). This optogenetic tool enables a short and spatially controlled activation of RhoA.…”

Deliver on Time or Pay the Fine: Scheduling in Membrane Trafficking

“…Nonetheless, recent technologies, such as optogenetic and proteolysis targeting chimera (PROTAC), are able to cope with such issues. While optogenetics allows light-dependent control of protein function with elevated spatio-temporal resolution (micrometer/millisecond), PROTAC involves drug-induced targeted protein degradation by redirecting the ubiquitin-proteasome system [53][54][55][56].…”

“…Optogenetic systems are built upon proteins that undergo conformational changes in response to light stimulation at specific wavelengths. Several optogenetic systems are available for researchers, which can be classified based on the number of subunits that are required for functionating, from monomer to multimer [56]. Optogenetic technology is currently employed in a variety of cell biology disciplines, ranging from cell signaling to gene regulation and phase separation to membrane trafficking.…”