PEX14

更新于：2025-05-07

基本信息

别名

Peroxin-14、peroxisomal biogenesis factor 14、Peroxisomal membrane anchor protein PEX14

+ [3]

简介

Component of the PEX13-PEX14 docking complex, a translocon channel that specifically mediates the import of peroxisomal cargo proteins bound to PEX5 receptor (PubMed:24235149, PubMed:28765278, PubMed:9653144). The PEX13-PEX14 docking complex forms a large import pore which can be opened to a diameter of about 9 nm (By similarity). Mechanistically, PEX5 receptor along with cargo proteins associates with the PEX14 subunit of the PEX13-PEX14 docking complex in the cytosol, leading to the insertion of the receptor into the organelle membrane with the concomitant translocation of the cargo into the peroxisome matrix (PubMed:24235149, PubMed:28765278). Plays a key role for peroxisome movement through a direct interaction with tubulin (PubMed:21525035).

关联

靶点

PEX14

作用机制

PEX14 inhibitors

在研机构

Helmholtz Zentrum München

原研机构

Helmholtz Zentrum München

在研适应症

锥虫病

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 PEX14 相关的临床结果

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100 项与 PEX14 相关的转化医学

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0 项与 PEX14 相关的专利（医药）

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203

项与 PEX14 相关的文献（医药）

2025-03-01·Free Radical Biology and Medicine

Salvianolic acid B drives gluconeogenesis and peroxisomal redox remodeling in cardiac ischemia/reperfusion injury: A metabolism regulation by metabolite signal crosstalk

Article

作者: Liu, Hai-Xin ; Qiao, Yuan-Biao ; Qi, Xiao-Ming ; Wang, Qi-Yan ; Li, Jin-Shan ; Zhang, Yuan-Lin ; Li, Qing-Shan ; Lin, Ji-Hui ; Liu, Jun-Yan ; Wu, Wei-Wei ; Ren, Jin-Hong ; Li, Qing-Fang

Cardiac metabolism relies on glycogen conversion by glycolysis. Glycolysis intersects fatty acid oxidation and often directs a signal crosstalk between redox metabolites. Myocardium with ischemia/reperfusion significantly diverts from normal metabolism. Prospectively, peroxisome lies central to metabolism and redox changes, but mechanisms underlying in ischemia/reperfusion remain undefined. This work aims at investigating the potential effects and mechanisms of Salvianolic acid B (Sal B) in cardioprotection through metabolic remodeling. Following experiments, we found that Sal B is absorbed in blood and rat hearts and its cardiac absorption prevents ischemia/reperfusion injury. Sal B cardioprotection relates to gluconeogenesis activation and peroxisomal redox remodeling. Gluconeogenesis compensates glycogen synthesis through upregulating pyruvate carboxylase (PC) and phosphoenolpyruvate carboxykinase. Gluconeogenic PC activity drives peroxisomal Pex2/Pex3 expressions and promotes the proliferation of peroxisome. Peroxisome quality control is enhanced with Pex5/Pex14/Pex13/Pex2 transcriptions. Nono, a non-POU domain-containing octamer-binding protein, promotes upregulation of gluconeogenic PC and peroxisomal gene transcripts through transcriptionally splicing their pre-RNAs at octamer duplex. Nono also controls the expression of SARM1/PARP1/sirtuin1 for catalyzing nicotinamide adenine dinucleotide (NAD⁺) consumption, leading to endurable redox capacities of peroxisome. Peroxisomal redox remodeling alters reactive oxygen species (ROS) and NAD⁺ contents, following which NAD⁺ affects cardiac accumulation of physiologically harmful glucocorticoid. In the tests of Sal B combinational treatments, results indicate ROS upregulation whereas NAD⁺ downregulation with glucocorticoid, ROS scavenging and glucocorticoid elimination with NAD⁺ precursor, and NAD⁺ promotion with ROS scavenger, respectively. This metabolite signal crosstalk alternatively antagonizes/agonizes Sal B cardioprotective functions on electrocardiographic output and infarction. Taken together, we reported a cardiac metabolism regulation with Sal B, capable of preventing myocardium from ischemia/reperfusion injury. The metabolite signal crosstalk was achieved by coupling reaction cascades between gluconeogenesis and peroxisomal redox remodeling.

2025-01-01·Developmental Cell

Outer mitochondrial membrane E3 Ub ligase MARCH5 controls de novo peroxisome biogenesis

Article

作者: Bippes, Claudia Christiane ; Neutzner, Albert ; Cartier, Etienne ; Karbowski, Mariusz ; Boyman, Liron ; Verhoeven, Nicolas ; Oshima, Yumiko

We report that the outer mitochondrial membrane (OMM)-associated E3 Ub ligase MARCH5 is vital for generating mitochondria-derived pre-peroxisomes. In human immortalized cells, MARCH5 knockout leads to the accumulation of immature peroxisomes, reduced fatty-acid-induced peroxisomal biogenesis, and abnormal peroxisome biogenesis in MARCH5/Pex14 and MARCH5/Pex3 dko cells. Upon fatty-acid-induced peroxisomal biogenesis, MARCH5 redistributes to peroxisomes, and ubiquitination activity-deficient mutants of MARCH5 accumulate on peroxisomes containing high levels of the OMM protein Tom20 (mitochondria-derived pre-peroxisomes). Similarly, depletion of peroxisome biogenesis factor Pex14 leads to the accumulation of MARCH5- and Tom20-positive pre-peroxisomes, whereas no peroxisomes are detected in MARCH5/Pex14 dko cells. Inconsistent with MARCH5 merely acting as a quality factor, mitochondrial decline is not evident in tested models. Furthermore, reduced expression of peroxisomal proteins is detected in MARCH5^-/- cells, whereas some of these proteins are stabilized in peroxisome biogenesis deficiency models lacking MARCH5 expression. Thus, MARCH5 is central for mitochondria-dependent peroxisome biogenesis.

2024-10-07·Journal of Cell Biology

A genome-wide screen links peroxisome regulation with Wnt signaling through RNF146 and TNKS/2

Article

作者: Tavasoli, Katherine U. ; Sheedy, Connor J. ; Vu, Jonathan T. ; Mandjikian, Lori ; Morrissey, Meghan A. ; Bacal, Julien ; Chowdhury, Soham P. ; Gardner, Brooke M. ; Richardson, Chris D.

Peroxisomes are membrane-bound organelles harboring metabolic enzymes. In humans, peroxisomes are required for normal development, yet the genes regulating peroxisome function remain unclear. We performed a genome-wide CRISPRi screen to identify novel factors involved in peroxisomal homeostasis. We found that inhibition of RNF146, an E3 ligase activated by poly(ADP-ribose), reduced the import of proteins into peroxisomes. RNF146-mediated loss of peroxisome import depended on the stabilization and activity of the poly(ADP-ribose) polymerases TNKS and TNKS2, which bind the peroxisomal membrane protein PEX14. We propose that RNF146 and TNKS/2 regulate peroxisome import efficiency by PARsylation of proteins at the peroxisome membrane. Interestingly, we found that the loss of peroxisomes increased TNKS/2 and RNF146-dependent degradation of non-peroxisomal substrates, including the β-catenin destruction complex component AXIN1, which was sufficient to alter the amplitude of β-catenin transcription. Together, these observations not only suggest previously undescribed roles for RNF146 in peroxisomal regulation but also a novel role in bridging peroxisome function with Wnt/β-catenin signaling during development.