Abstract:In peroxisomal matrix protein import two processes directly depend on the binding and hydrolysis of ATP, both taking place at the late steps of the peroxisomal import cycle. First, ATP hydrolysis is required to initiate a ubiquitin-transfer cascade to modify the import (co-)receptors. These receptors display a dual localization in the cytosol and at the peroxisomal membrane, whereas only the membrane bound fraction receives the ubiquitin modification. The second ATP-dependent process of the import cycle is car… Show more
“…With respect to matrix protein import, the processes of cargo translocation and receptor recycling are still debated (reviewed in Francisco et al 2017 ). Progress has been made in the understanding of the unique structure and molecular function of the peroxisomal AAA–ATPase Pex1/Pex6 complex, which is involved in the export and recycling of the ubiquitinated import receptors Pex5 and Pex7 (Ciniawsky et al 2015 ; Blok et al 2015 ; reviewed in Schwerter et al 2017 ) (Figs. 1 , 2 ).…”
Section: Mysterious Machinery: New Proteins and Functions At The Peromentioning
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.
“…With respect to matrix protein import, the processes of cargo translocation and receptor recycling are still debated (reviewed in Francisco et al 2017 ). Progress has been made in the understanding of the unique structure and molecular function of the peroxisomal AAA–ATPase Pex1/Pex6 complex, which is involved in the export and recycling of the ubiquitinated import receptors Pex5 and Pex7 (Ciniawsky et al 2015 ; Blok et al 2015 ; reviewed in Schwerter et al 2017 ) (Figs. 1 , 2 ).…”
Section: Mysterious Machinery: New Proteins and Functions At The Peromentioning
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.
“…Peroxisome biogenesis requires the generation of a membrane and subsequent targeting and insertion of peroxisomal membrane proteins (PMPs) into the lipid bilayer, and import of soluble enzymes into the peroxisomal matrix [ 56 , 57 ]. Unlike mitochondria, peroxisomes do not contain DNA or protein synthesis machinery, and have to import all soluble proteins post-translationally from the cytosol.…”
Section: Introductionmentioning
confidence: 99%
“…These findings highlight the importance of peroxisome plasticity and regulation of peroxisome number in health and disease and underline that peroxisomes, which contribute to ROS homeostasis, breakdown of toxic lipids and combat of pathogens, have important protective functions (Box 1). Peroxisome biogenesis and functionPeroxisome biogenesis requires the generation of a membrane and subsequent targeting and insertion of peroxisomal membrane proteins (PMPs) into the lipid bilayer, and import of soluble enzymes into the peroxisomal matrix [56, 57]. Unlike mitochondria, peroxisomes do not contain DNA or protein synthesis machinery, and have to import all soluble proteins post-translationally from the cytosol.…”
Peroxisome biogenesis is governed by molecular machineries, which are either unique to peroxisomes or are partially shared with mitochondria. As peroxisomes have important protective functions in the cell, modulation of their number is important for human health and disease. Significant progress has been made towards our understanding of the mechanisms of peroxisome formation, revealing a remarkable plasticity of the peroxisome biogenesis pathway. Here we discuss most recent findings with particular focus on peroxisome formation in mammalian cells.
“…These results are described in Schwerter et al (2017), Bittner et al (2017) and Reidick et al (2017). The GTP-and ATP-dependent membrane processes were bridged by a central Project Z addressing proteome analysis, see the contribution by Lindemann et al (2017).…”
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