Highlight: organelles on and off the map: diversity, specialization and subdomains

A century ago, and then popularized in the 1960s, the formal distinction between eukaryotes and other forms of life was made (Sapp 2005). While the categorization originally focussed on cells with or without nuclei, today, each and every person who starts their journey in cell biology learns that the presence of organelles is what defines a eukaryotic cell. The striking and elaborate morphology of these organelles was already visualized by electron microscopy in the middle of the previous century. This work culminated in a Nobel Prize to Albert Claude, Christian de Duve, and George E. Palade in 1974. Yet, despite this, it feels like we are still at the tip of the iceberg in fully understanding the different organelles, their organizational complexity, and, in particular, their relationships between each other.

The world of organelle biology has been propelled forward by the cumulative effort, curiosity and collaboration of countless labs around the globe. One of these is the laboratory of Maya Schuldiner at the Weizmann Institute of Science. Through conceptually bold and methodologically innovative science and the most elegant use of yeast genetics, she has contributed to ground-breaking discoveries, which have shaped our community’s view and understanding on organelle identity, function and interconnectivity (Figure 1). Work from the Schuldiner laboratory extended a fundamental paradigm in cell biology by characterizing contact sites between organelles, including those that do not involve the endoplasmic reticulum. Their discoveries have dramatically increased the number of known organelle contact sites, defined the tethers that form them, and identified regulators and the interplay between contacts and lipids (Castro et al. 2022; Eisenberg-Bord et al. 2021; Shai et al. 2018). In parallel, Maya’s lab, together with collaborators, also uncovered fundamental machineries and pathways that are required to target proteins from the cytosol to unique subcellular membranes (Aviram et al. 2016; Hansen et al. 2018; Rosenthal et al. 2020). Collectively, these landmark studies have opened new avenues for understanding cellular function and dysfunction.

Figure 1:

Cartography of the subcellular world.

Maya is as brilliant as a colleague as she is as a scientist, and we cherish the opportunities we have had to work closely with her and to experience her mentorship and friendship. To honour her, we present this Highlight Issue of Biological Chemistry. Inside are review articles which explore new discoveries on specialized organelles, organelle subdomains and contacts, protein targeting to organelles with complex sub-compartmentalization, and methods to study these. Altogether, they demonstrate how recent breakthroughs move away from a simplistic view of an organelle as a homogeneous functional unit and highlight the true complexity of cellular organization.

Yury Bykov and Emma Fenech thank all authors for contributing their insightful perspectives on the presented organellar-centric topics. We would also like to extend our thanks to De Gruyter Brill Publishers and the Managing Editor of Biological Chemistry, Torsten Krüger, for supporting and helping us in assembling this collection.