Proliferation and fission of peroxisomes — An update

Abstract

In mammals, peroxisomes perform crucial functions in cellular metabolism, signalling and viral defense which are essential to the health and viability of the organism. In order to achieve this functional versatility peroxisomes dynamically respond to molecular cues triggered by changes in the cellular environment. Such changes elicit a corresponding response in peroxisomes, which manifests itself as a change in peroxisome number, altered enzyme levels and adaptations to the peroxisomal structure. In mammals the generation of new peroxisomes is a complex process which has clear analogies to mitochondria, with both sharing the same division machinery and undergoing a similar division process. How the regulation of this division process is integrated into the cell's response to different stimuli, the signalling pathways and factors involved, remains somewhat unclear. Here, we discuss the mechanism of peroxisomal fission, the contributions of the various division factors and examine the potential impact of post-translational modifications, such as phosphorylation, on the proliferation process. We also summarize the signalling process and highlight the most recent data linking signalling pathways with peroxisome proliferation.

A role for Mitochondrial Rho GTPase 1 (MIRO1) in motility and membrane dynamics of peroxisomes

“…These membrane alterations are suggested to contribute to peroxisome formation via division of elongated organelles, and to enable organelle crosstalk 1, 48. To what extent microtubule motors and pulling forces contribute to peroxisome membrane dynamics is unclear, as peroxisome elongation is unexpectedly promoted by microtubule‐depolymerising drugs, and peroxisome division can occur in the absence of microtubules 9, 49.…”

“…Peroxisome proliferation in those cells is likely impaired due to reduced division rates (eg, due to altered peroxisomal membrane lipid composition). Whereas expression of MIRO1 cannot fully restore division, this can be achieved by PEX11β, a key factor in peroxisomal membrane remodelling and division1 (Figure 5A). Expression of PEX11β‐EGFP in PEX5 deficient cells promoted peroxisome elongation and subsequent division (Figure 5A) confirming earlier reports that PEX11β‐induced peroxisome proliferation is independent of peroxisomal metabolism 45, 54.…”

“…Peroxisomes are dynamic, multifunctional organelles that vary in size, number and shape depending on cell type, environmental stimuli and metabolic demand,1 but the underlying molecular mechanisms which govern this versatility are not fully understood. Similar to mitochondria, peroxisomes are oxidative organelles that fulfil important functions in lipid metabolism and ROS homeostasis rendering them essential for human health and development 2, 3.…”

The Peroxisome-Mitochondria Connection: How and Why?

“…Peroxisomes and mitochondria can proliferate by fission of pre-existing organelles [42,43,44]. A major breakthrough in the field was the discovery that these organelles share multiple components of their fission machinery (e.g., mitochondrial fission protein (FIS) 1 [45], mitochondrial fission factor (MFF) [46], ganglioside-induced differentiation-associated protein (GDAP) 1 [47], and dynamin 1-like protein (DNM1L) [48,49]) (Figure 1c).…”

Building Bridges - Organelle Tethering Complexes in Subcellular Communication

“…Mitochondria and peroxisomes share an intricate relationship and cooperate in a significant number of metabolic functions such as fatty acid degradation or maintenance of cellular ROS homeostasis [19]. Both organelles also share a significant part of their division machinery, which may mirror the demand for a coordinated biogenesis under distinct metabolic conditions [20]. Division proteins shared by peroxisomes and mitochondria include the dynamin-like fission GTPase DLP1/Drp1, and the membrane adaptor proteins Fis1 (Fission factor 1) and Mff (Mitochondrial fission factor), which can recruit DLP1 to the organelle membranes.…”