Determinants of Peroxisome Membrane Dynamics.

Michael Schrader,Ruth E Carmichael

doi:10.3389/fphys.2022.834411

Abstract

Organelles within the cell are highly dynamic entities, requiring dramatic morphological changes to support their function and maintenance. As a result, organelle membranes are also highly dynamic, adapting to a range of topologies as the organelle changes shape. In particular, peroxisomes—small, ubiquitous organelles involved in lipid metabolism and reactive oxygen species homeostasis—display a striking plasticity, for example, during the growth and division process by which they proliferate. During this process, the membrane of an existing peroxisome elongates to form a tubule, which then constricts and ultimately undergoes scission to generate new peroxisomes. Dysfunction of this plasticity leads to diseases with developmental and neurological phenotypes, highlighting the importance of peroxisome dynamics for healthy cell function. What controls the dynamics of peroxisomal membranes, and how this influences the dynamics of the peroxisomes themselves, is just beginning to be understood. In this review, we consider how the composition, biophysical properties, and protein-lipid interactions of peroxisomal membranes impacts on their dynamics, and in turn on the biogenesis and function of peroxisomes. In particular, we focus on the effect of the peroxin PEX11 on the peroxisome membrane, and its function as a major regulator of growth and division. Understanding the roles and regulation of peroxisomal membrane dynamics necessitates a multidisciplinary approach, encompassing knowledge across a range of model species and a number of fields including lipid biochemistry, biophysics and computational biology. Here, we present an integrated overview of our current understanding of the determinants of peroxisome membrane dynamics, and reflect on the outstanding questions still remaining to be solved.

Highlights

Peroxisomes are multifunctional, oxidative organelles with key functions in cellular redox and lipid metabolism, which impact on human health and disease (Islinger et al, 2018)
PEX11α knock-out mice are viable and show normal peroxisome abundance (Li et al, 2002a), but feeding a high-fat diet increased the rate of de novo lipogenesis, dyslipidaemia and obesity, decreased fatty acid β-oxidation and led to impaired physical activity and energy expenditure (Chen et al, 2019). These findings indicate that PEX11α and PEX11β differ in function, and may support a role for PEX11α in peroxisomal fatty acid metabolism rather than in peroxisome dynamics
In addition to being morphologically distinct, spherical and tubular peroxisomal membrane compartments differ in the localisation of peroxisomal matrix and membrane proteins. Membrane proteins, such as PEX11β, FIS1 as well as the early peroxins PEX3, PEX16 and PEX19 involved in membrane protein targeting/insertion were observed to localise to the tubular domains induced by PEX11β expression, whereas matrix enzymes and membrane proteins with a metabolic function preferentially localised to the spherical domains (Delille et al, 2010)

Summary

Introduction

Peroxisomes are multifunctional, oxidative organelles with key functions in cellular redox and lipid metabolism, which impact on human health and disease (Islinger et al, 2018). Membrane expansion/elongation (growth), membrane constriction and subsequent fission leading to the formation of new peroxisomes that import matrix and membrane proteins to retain functionality (for detailed reviews, see Nuttall et al, 2011; Costello and Schrader, 2018; Islinger et al, 2018).

Results

Conclusion