The cytoplasm of every eukaryotic cell is elaborately subdivided into discrete, specialized, membrane-bound structures called organelles. Each organelle has a char- acteristic morphology and is equipped with a specific set of proteins and lipids to create a microenvironment that is elegantly suited to carry out its defined functions in a cell 1–4 . The different organelles communicate through a constant exchange of material that, although enhancing the metabolic efficiency of cells, does not compromise each organelle’s steady-state composition and identity 5 . The complexity in both the architecture and function of organelles makes it energetically unfavourable for cells to rapidly manufacture organelles de novo, even in the case of organelles that originate from other intracellular compartments 3,6 . Rather, a template-based biogenesis mechanism involving the growth and division of pre- existing organelles is the preferred method of maintain- ing organelle populations during cell proliferation. With each round of cell division, cells duplicate and apportion their various organelles to the two resulting cells with high accuracy, a process called organelle inheritance 1 . In the past decade, considerable advances have been made in understanding the molecular mecha- nisms of organelle inheritance using the budding yeast Saccharomyces cerevisiae. S. cerevisiae has facilitated the study of organelle inheritance because its growth is highly polarized, with a mother cell forming a bud that is initially much smaller than itself. At first glance it would seem that cells that divide by median fission (for example, mammalian cells) need only to disperse their organelles randomly in the cytoplasm to achieve organelle inheritance on cytokinesis; however, organelle partitioning in these cells has also been shown to be an ordered process involving the cytoskeleton and motor proteins 7–12 . This Review highlights the recent progress made in uncovering the molecular basis of perox- isome inheritance in yeast; however, we do not hesitate to diverge from the field of peroxisome inheritance to draw the reader’s attention to fascinating complemen- tary findings arising from studies of inheritance of other organelles. One emergent theme is that, although each organelle uses specific molecular components to ensure its inheritance by future generations of cells, a set of fundamental rules applies to the mechanisms of inheritance of all organelles. The timing of this Review coincides with an unprecedented understanding of these common denominators, leading to the formulation of unifying themes and testable general paradigms for the partitioning of all organelles. Organelle inheritance in budding yeast S. cerevisiae multiplies by a repetitive pattern of growth and division termed budding. At the beginning of each cell cycle, cells select a site for bud emergence based on physical cues from previous cell cycles 13,14 . Among the signalling molecules and polarity-establishing factors attracted to this future bud site is a conserved class of proteins called formins 14,15 . Formins function in assembling unbranched actin filaments by holding on to the plus end of an actin filament while catalysing the incorporation of new actin monomers 16–19 . As formins are strategically positioned at the future bud site, they Department of Cell Biology, University of Alberta, Medical Sciences Building 5-14, Edmonton, Alberta, T6G 2H7, Canada. Correspondence to R.A.R e-mail: rick.rachubinski@ ualberta.ca doi:10.1038/nrm2960 Published online 18 August 2010 Formin One of a group of conserved proteins that nucleate actin assembly by promoting the incorporation of new actin monomers into the growing plus end of an actin filament, with which they remain associated. Actin monomer A monomer of actin (also known as globular actin (G-actin)) that polymerizes into helical actin filaments called filamentous actin (F-actin) or microfilaments. Molecular mechanisms of organelle inheritance: lessons from peroxisomes in yeast Andrei Fagarasanu, Fred D. Mast, Barbara Knoblach and Richard A. Rachubinski Abstract | Preserving a functional set of cytoplasmic organelles in a eukaryotic cell requires a process of accurate organelle inheritance at cell division. Studies of peroxisome inheritance in yeast have revealed that polarized transport of a subset of peroxisomes to the emergent daughter cell is balanced by retention mechanisms operating in both mother cell and bud to achieve an equitable distribution of peroxisomes between them. It is becoming apparent that some common mechanistic principles apply to the inheritance of all organelles, but at the same time, inheritance factors specific for each organelle type allow the cell to differentially and specifically control the inheritance of its different organelle populations. REVIEWS 644 | SEPTEMBER 2010 | VOLUME 11 www.nature.com/reviews/molcellbio © 20 Macmillan Publishers Limited. All rights reserved 10