Kinase MPK17 and the Peroxisome Division Factor PMD1 Influence Salt-induced Peroxisome Proliferation

Elizabeth M. Frick; Lucia C. Strader

doi:10.1104/pp.17.01019

PEX11α Is Required for Peroxisome Proliferation in Response to 4-Phenylbutyrate but Is Dispensable for Peroxisome Proliferator-Activated Receptor Alpha-Mediated Peroxisome Proliferation

Molecular and Cellular Biology ◽

10.1128/mcb.22.23.8226-8240.2002 ◽

2002 ◽

Vol 22 (23) ◽

pp. 8226-8240 ◽

Cited By ~ 98

Author(s):

Xiaoling Li ◽

Eveline Baumgart ◽

Gao-Xiang Dong ◽

James C. Morrell ◽

Gerardo Jimenez-Sanchez ◽

...

Keyword(s):

Membrane Proteins ◽

Gene Overexpression ◽

Peroxisome Proliferator ◽

Peroxisome Proliferation ◽

Peroxisomal Membrane ◽

Peroxisome Proliferator Activated Receptor ◽

Physiological Functions ◽

Peroxisomal Protein ◽

Receptor Alpha ◽

Peroxisome Division

ABSTRACT The PEX11 peroxisomal membrane proteins promote peroxisome division in multiple eukaryotes. As part of our effort to understand the molecular and physiological functions of PEX11 proteins, we disrupted the mouse PEX11α gene. Overexpression of PEX11α is sufficient to promote peroxisome division, and a class of chemicals known as peroxisome proliferating agents (PPAs) induce the expression of PEX11α and promote peroxisome division. These observations led to the hypothesis that PPAs induce peroxisome abundance by enhancing PEX11α expression. The phenotypes of PEX11α−/− mice indicate that this hypothesis remains valid for a novel class of PPAs that act independently of peroxisome proliferator-activated receptor alpha (PPARα) but is not valid for the classical PPAs that act as activators of PPARα. Furthermore, we find that PEX11α−/− mice have normal peroxisome abundance and that cells lacking both PEX11α and PEX11β, a second mammalian PEX11 gene, have no greater defect in peroxisome abundance than do cells lacking only PEX11β. Finally, we report the identification of a third mammalian PEX11 gene, PEX11γ, and show that it too encodes a peroxisomal protein.

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OXPHOS deficiencies affect peroxisome proliferation by downregulating genes controlled by the SNF1 signaling pathway

10.1101/2021.08.23.457403 ◽

2021 ◽

Author(s):

Jean-Claude Farre ◽

Krypton Carolino ◽

Lou Devanneaux ◽

Suresh Subramani

Keyword(s):

Redox Balance ◽

Atp Depletion ◽

Environmental Cues ◽

Peroxisome Proliferation ◽

Methanol Metabolism ◽

Cellular Redox ◽

Atp Production ◽

Physiological Relevance ◽

Peroxisome Division ◽

Mitochondrial Uncoupler

How environmental cues influence peroxisome proliferation, particularly through other organelles, remains largely unknown. Yeast peroxisomes metabolize all fatty acids (FA), and methylotrophic yeasts also metabolize methanol. NADH and acetyl-CoA, the products of these pathways enter mitochondria for ATP production, and for anabolic reactions. During the metabolism of FA and/or methanol, the mitochondrial oxidative phosphorylation (OXPHOS) pathway accepts NADH for ATP production and maintains cellular redox balance. Remarkably, peroxisome proliferation in Pichia pastoris was abolished in NADH shuttling and OXPHOS mutants affecting complex I or III, or by the mitochondrial uncoupler, 2,4-dinitrophenol (DNP), indicating ATP depletion causes the phenotype. We show that mitochondrial OXPHOS deficiency inhibits the expression of several peroxisomal proteins implicated in FA and methanol metabolism, as well as in peroxisome division and proliferation. These genes are regulated by the Snf1 complex (SNF1), a pathway generally activated by high AMP and low ATP. Consistent with this mechanism, in OXPHOS mutants, Snf1 is activated by phosphorylation, but Gal83, its interacting subunit, fails to translocate to the nucleus. Phenotypic defects in peroxisome proliferation observed in the OXPHOS mutants, and phenocopied by the Δgal83 mutant, were rescued by deletion of three transcriptional repressor genes (MIG1, MIG2 and NRG1) controlled by SNF1 signaling. We uncovered here the mechanism by which peroxisomal and mitochondrial metabolites influence redox and energy metabolism, while also influencing peroxisome biogenesis and proliferation, thereby exemplifying interorganellar communication and interplay involving peroxisomes, mitochondria, cytosol and the nucleus. We discuss the physiological relevance of this work in view of human OXPHOS deficiencies.

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Peroxisome proliferation: Organelles or activity as an endpoint?

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100147818 ◽

1993 ◽

Vol 51 ◽

pp. 396-397

Author(s):

Catherine A. Taylor ◽

Bruce M. Jarnot

Keyword(s):

Acid Oxidation ◽

Peroxisome Proliferation ◽

Post Dose ◽

Oxidation Activity ◽

Wasting Syndrome ◽

Perfluorodecanoic Acid ◽

Hypolipidemic Agent ◽

Commercially Important ◽

Acyl Coa Oxidase ◽

Mitochondrial Disruption

Peroxisome induction can be expressed as an increase in peroxisome area (proliferation) or as an increase in peroxisomal fatty acid oxidation (activity). This study compares proliferation and activity as endpoints for hepatic peroxisome induction by perfluorodecanoic acid (PFDA). Fluorocarboxylic acids such as PFDA represent a class of compounds possessing commercially important surfactant properties. A single 50 mg/Kg ip. dose of PFDA produces a characteristic “wasting syndrome” in male F-344 rats. Symptoms include hypophagia, weight loss, hepatomegaly, and delayed lethality. Hepatic studies reveal changes similar to those seen with the hypolipidemic agent clofibrate. These include mitochondrial disruption, endoplasmic reticulum and peroxisome proliferation, and increased peroxisomal acyl-CoA oxidase activity.Male Fisher-344 rats received a single ip. dose of 2, 20, or 50mg/Kg PFDA dissolved in 1:1 propylene glycol/water and were sacrificed 8 days post-dose. All control rats received an equal volume of vehicle ip. Animals were provided food and water ad libitum, except pair-fed controls which received the same restrictive food intake consumed by their weight-paired dosed partners (50mg/Kg PFDA group) to simulate the hypophagia associated with PFDA.

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Faculty Opinions recommendation of Peroxisome proliferation-associated control of reactive oxygen species sets melanocortin tone and feeding in diet-induced obesity.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.13306991.14688090 ◽

2011 ◽

Author(s):

Virginia Brooks ◽

Belinda H McCully

Keyword(s):

Reactive Oxygen Species ◽

Reactive Oxygen ◽

Peroxisome Proliferation ◽

Oxygen Species ◽

Diet Induced Obesity

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Phthalate Esters, Cystic Kidney Disease in Animals and Possible Effects on Human Health: A Review

Human & Experimental Toxicology ◽

10.1177/096032719000900607 ◽

1990 ◽

Vol 9 (6) ◽

pp. 397-401 ◽

Cited By ~ 17

Author(s):

K.N. Woodward

Keyword(s):

Kidney Disease ◽

Human Health ◽

Phthalate Esters ◽

Renal Cysts ◽

Cystic Kidney Disease ◽

Cystic Kidney ◽

Peroxisome Proliferation ◽

Peroxisome Proliferators ◽

Prolonged Administration ◽

Route Of Exposure

1 Phthalate esters are known to cause hepatic peroxisome proliferation in rodents and, after prolonged administration, hepatocarcinogenesis. Peroxisome proliferators as a group are hepatocarcinogenic. The mechanism is not known but it does not appear to involve a direct genotoxic element. 2 DEHP and DBP have been shown to cause renal cysts in rodents and they also produce renal peroxisome proliferation. There are no data to causally link the two phenomena. 3 Although renal cysts have been noted in haemodialysis patients and haemodialysis is a route of exposure to DEHP, there are no data to suggest a cause and effect relationship. 4 More studies are needed on the mechanism of renal cystogenesis.

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