Morphology and function of membrane-bound organelles
Introduction
Organelles are dynamic, changing size and shape to maintain homeostasis and adjusting to the various needs of the cell. Some changes occur as part of the normal cell cycle, for example during cell division [1, 2, 3]. Other changes happen in response to challenges or stress and reflect a modification in organelle function, such as a change in protein folding capacity of the endoplasmic reticulum (ER) or ATP production in mitochondria [4, 5]. It is assumed that alterations to organelle morphology reflect an underlying functional optimization. Yet, this relationship is often poorly understood: for example, does the peripheral endoplasmic reticulum (ER) have to be in the shape of tubules in order to carry out its function? Does mitochondrial size matter? In this review we discuss recent advances in our understanding of the relationship between organelle structure and function, focusing primarily on the ER, nucleus and mitochondria. The reader is referred to excellent reviews that cover earlier work on Golgi [1], peroxosime [6] and endosome [7] structure.
Section snippets
Shaping a membrane-bound organelle
How are organelles shaped? The morphology of most organelles is characterized by a combination of flat and curved membrane, such as in the ER (Figure 1a). Cellular membranes are lipid bilayers made predominantly of phospholipids and proteins, both of which can contribute to membrane curvature. A difference in lipid composition between the two bilayers can itself lead to membrane curvature, and this likely drives the formation of the rims of Golgi cisternae and the tubular structures that
Complex shapes allow for distinct functions within a single organelle
While some organelles, such as the nucleus or the vacuole, are simple in shape, other organelles, such as the Golgi and the ER, have complex shapes made up of a network of cisternae and tubules. This complexity allows for segregation of biochemical processes within the organelle: for example, ribosomes are preferentially associated with the flat ER membrane that forms the rough ER [14•, 18]. In contrast, ER tubules are engaged in processes such as lipid synthesis and they are responsible for
Organelle shape and cell function
It is likely that organelle shape, and in particular the membrane configuration, has evolved to suit not only the organelle's biological activity, but also overall cell function. The formation of MCS discussed above is one such example, and recent studies suggest that the reticular nature of the peripheral ER is also important to allow passage of macromolecules from the cytosol to the plasma membrane. In fission yeast, for example, the localization of a plasma membrane protein, Mid1, which
Changing shape in adaptation to stress
In addition to changes associated with the cell cycle, cells may experience a need to increase the functional capacity of an organelle, either due to specialization following differentiation or under stress conditions, when the activity of a certain cellular compartment must be increased in order achieve homeostasis. A well-documented case is the unfolded protein response (UPR), which is activated due to the accumulation of unfolded proteins in the ER and leads to increased phospholipid
The importance of organelle size
In addition to having a distinct shape, organelles also have a specific size. Organelle size may scale with cell size as was shown in yeast for the nucleus [38, 39] and more recently for mitochondria [40•]. Organelle size may also expand to accommodate the cell's changing needs, as in the case of ER expansion during the UPR or when mitochondria fuse to evade autophagy, described above. Thus, the size of an organelle undoubtedly affects its function, but in only very few cases has organelle size
Conclusions
In this review we presented examples of the relationship between organelles, their surrounding membranes and morphology, and their function. In describing recent studies, we highlighted some of the possible mechanisms determining organelle shape, as well as the functional consequences of altering their structure. Organelles differ in shape because the lipid and protein building blocks involved in determining membrane shape are distinct, resulting in the prototypical organelle shape we see by
References and recommended reading
Papers of particular interest, published within the period of review, have been highlighted as:
• of special interest
•• of outstanding interest
Acknowledgements
We thank Will Prinz, Rebecca Meseroll and Alison Walters for excellent comments on the manuscript, and apologize for all those whose work could not be cited due to space limitations.
RH is supported by NIH: R01 GM057839 and GM098766. OCF is supported by intramural funding from NIDDK.
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