No peroxisome is an island - Peroxisome contact sites

Abstract

In order to optimize their multiple cellular functions, peroxisomes must collaborate and communicate with the surrounding organelles. A common way of communication between organelles is through physical membrane contact sites where membranes of two organelles are tethered, facilitating exchange of small molecules and intracellular signaling. In addition contact sites are important for controlling processes such as metabolism, organelle trafficking, inheritance and division. How peroxisomes rely on contact sites for their various cellular activities is only recently starting to be appreciated and explored and the extent of peroxisomal communication, their contact sites and their functions are less characterized. In this review we summarize the identified peroxisomal contact sites, their tethering complexes and their potential physiological roles. Additionally, we highlight some of the preliminary evidence that exists in the field for unexplored peroxisomal contact sites.

Keywords: Chloroplast; Endoplasmic reticulum; Lipid droplet; Membrane contact site; Mitochondria; Peroxisome.

Fig. 1

Peroxisome–ER contact site. Peroxisomes have been shown to create two types of contact sites with the endoplasmic reticulum (ER): (A) Contacts required for regulated inheritance: in the budding yeast, to enable a fraction of peroxisomes to be actively retained in the mother cell, they are anchored to the cortical ER by a tethering complex consisting of ER-bound Pex3 and peroxisomal Pex3 connecting through the cytosolic Inp1. To enable active inheritance of a certain subpopulation into the bud, peroxisomes that harbor Inp2 interact with the myosin motor Myo2 triggering movement of the peroxisome along actin cables directionally to the bud. (B) Contacts required for proliferation: in the budding yeast, the membrane protein Pex30 interacts with the reticulon homology proteins Rtn1, Rtn2 and Yop1. The Pex30 protein complex acts as a hub for the regulation of peroxisome proliferation and movement.

Fig. 2

Peroxisome–mitochondria contact site. Peroxisomes can be localized adjacent to a specific mitochondrial niche near the ER-mitochondria contact site proximal to where the pyruvate dehydrogenase (PDH) complex is found in the mitochondria matrix. The proximity to the ER-mitochondria contacts may suggest a function of a three way organelle junction. The peroxisome-mitochondria tether has been suggested to be mediated by the interaction between Pex11, a key protein involved in peroxisome proliferation, and Mdm34, one of the proteins creating the ER-mitochondria tether (ERMES).

Fig. 3

Peroxisome–chloroplast contact site. In Arabidopsis thaliana, upon exposure to light, peroxisomes increase their contact sites with chloroplasts to facilitate the transfer of photorespiration metabolites. During light conditions, peroxisomes also change their morphology to an elliptical shape potentially to increase the area and strength of the contacts. The mechanism for tethering is through the Zn RING finger of Pex10 and an unknown counterpart on the chloroplast.

Fig. 4

Peroxisome–lipid droplet contact site. In the budding yeast, peroxisomes stably adhere to lipid droplets (LDs) thereby stimulating the breakdown and transfer of various lipids across these organellar boundaries. Peroxisome protrusions, termed pexopodia, have been seen to invade the LD core as a result of hemifusion of the single leaflet of the lipid droplet membrane and the outer leaflet of the peroxisomal membrane. Pexopodia are believed to facilitate the flux of fatty acids into peroxisomes and the transfer of peroxisomal oxidation enzymes into LDs.

Fig. 5

Peroxisome–peroxisome interaction. In mammalian cells, peroxisomes are engaged in close self-interactions. Although such interactions are transient, peroxisomes are able to re-contact rapidly creating long-term contacts. The interaction between peroxisomes has three possible roles: (A) Movement of peroxisome populations in the cell. (B) Fusion between peroxisomes. (C) Creation of functional units to exchange metabolites or lipids.

Fig. 6

Peroxisome–lysosome contact site. It was recently identified that a peroxisome–lysosome contact site occurs (termed LPMC) in human cells. The LPMC is dynamic and cholesterol dependent. The tether holding the two organelles together is the integral lysosomal membrane protein, Synaptotagmin VII (Syt7), through binding to the lipid PI(4,5)P₂ on the peroxisomal membrane. This contact site facilitates the transfer of cholesterol from lysosomes to peroxisomes.

Fig. 7

Peroxisome contact site formation. Three hypotheses as to how peroxisomes maintain such diverse contacts with other organelles: (A) Random encounters: peroxisome may contain all the necessary proteins, lipids and molecules to interact with any other organelle and even with multiple organelles at once. Random encounters enable the creation of contact sites between peroxisomes and other organelles. (B) Conditional contact sites: peroxisome contact sites are condition dependent hence forming specifically with certain organelles for specific functions. Changes in contact site partners are enabled by specific signals for the regulation of the tether/proteins/lipids. (C) Specialized peroxisomes: peroxisome subpopulations exist in the cell, each tailored to interact with a specific organelle. Each subpopulation could contain a unique proteome and has the ability to interact with a specific organelle for a different function.