The peroxisome: an update on mysteries 2.0

Markus Islinger,Michael Schrader,H Dariush Fahimi,Alfred Voelkl

doi:10.1007/s00418-018-1722-5

Abstract

Peroxisomes are key metabolic organelles, which contribute to cellular lipid metabolism, e.g. the β-oxidation of fatty acids and the synthesis of myelin sheath lipids, as well as cellular redox balance. Peroxisomal dysfunction has been linked to severe metabolic disorders in man, but peroxisomes are now also recognized as protective organelles with a wider significance in human health and potential impact on a large number of globally important human diseases such as neurodegeneration, obesity, cancer, and age-related disorders. Therefore, the interest in peroxisomes and their physiological functions has significantly increased in recent years. In this review, we intend to highlight recent discoveries, advancements and trends in peroxisome research, and present an update as well as a continuation of two former review articles addressing the unsolved mysteries of this astonishing organelle. We summarize novel findings on the biological functions of peroxisomes, their biogenesis, formation, membrane dynamics and division, as well as on peroxisome–organelle contacts and cooperation. Furthermore, novel peroxisomal proteins and machineries at the peroxisomal membrane are discussed. Finally, we address recent findings on the role of peroxisomes in the brain, in neurological disorders, and in the development of cancer.

Highlights

The interest in peroxisomes and theirphysiological roles in health and disease is constantly increasing within the scientific community, and there is no doubt that peroxisomes are on the rise
In addition to the most prevalent disorder, X-linked adrenoleukodystrophy (X-ALD), which is evoked by mutations in the peroxisomal fatty acid transporter ABCD1 (Fig. 1), important SEDs with a severe brain pathology are caused by mutations in the genes of acyl-CoA oxidase 1 (ACOX1) and the multifunctional protein 2 (MFP2, encoded by HSD17B4) (Berger et al 2016)
With regard to protein import, new peroxins and alternative import pathways have been identified and progress has been made in the understanding of the export and recycling of the ubiquitinated import receptors Pex5 and Pex7 via the Pex1/Pex6 complex

Summary

Introduction

The interest in peroxisomes and their (patho)physiological roles in health and disease is constantly increasing within the scientific community, and there is no doubt that peroxisomes are on the rise. Many of those TA proteins, which act as membrane adaptors for important, disease-relevant cellular processes, are shared with mitochondria (see “Mysterious multiplication: new insights into peroxisome division” and “Peroxisome–organelle interactions: the mysterious world of tethers”) (Schrader et al 2015a, b) (Fig. 1, 2).

Results

Conclusion