Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Pex35 is a regulator of peroxisome abundance.

ABSTRACT: Peroxisomes are cellular organelles with vital functions in lipid, amino acid and redox metabolism. The cellular formation and dynamics of peroxisomes are governed by PEX genes; however, the regulation of peroxisome abundance is still poorly understood. Here, we use a high-content microscopy screen in Saccharomyces cerevisiae to identify new regulators of peroxisome size and abundance. Our screen led to the identification of a previously uncharacterized gene, which we term PEX35, which affects peroxisome abundance. PEX35 encodes a peroxisomal membrane protein, a remote homolog to several curvature-generating human proteins. We systematically characterized the genetic and physical interactome as well as the metabolome of mutants in PEX35, and we found that Pex35 functionally interacts with the vesicle-budding-inducer Arf1. Our results highlight the functional interaction between peroxisomes and the secretory pathway.

SUBMITTER: Yofe I

PROVIDER: S-EPMC7611368 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Pex35 is a regulator of peroxisome abundance.

Yofe Ido I Soliman Kareem K Chuartzman Silvia G SG Morgan Bruce B Weill Uri U Yifrach Eden E Dick Tobias P TP Cooper Sara J SJ Ejsing Christer S CS Schuldiner Maya M Zalckvar Einat E Thoms Sven S

Journal of cell science 20170103 4

Peroxisomes are cellular organelles with vital functions in lipid, amino acid and redox metabolism. The cellular formation and dynamics of peroxisomes are governed by PEX genes; however, the regulation of peroxisome abundance is still poorly understood. Here, we use a high-content microscopy screen in Saccharomyces cerevisiae to identify new regulators of peroxisome size and abundance. Our screen led to the identification of a previously uncharacterized gene, which we term PEX35 ...[more]

PMID: 28049721

Similar Datasets

Phosphorylation-dependent activation of peroxisome proliferator protein PEX11 controls peroxisome abundance.

Project description:Peroxisomes are dynamic organelles that divide continuously in growing cell cultures and expand extensively in lipid-rich medium. Peroxisome population control is achieved in part by Pex11p-dependent regulation of peroxisome size and number. Although the production of Pex11p in yeast is tightly linked to peroxisome biogenesis by transcriptional regulation of the PEX11 gene, it remains unclear if and how Pex11p activity could be modulated by rapid signaling. We report the reversible phosphorylation of Saccharomyces cerevisiae Pex11p in response to nutritional cues and delineate a mechanism for phosphorylation-dependent activation of Pex11p through the analysis of phosphomimicking mutants. Peroxisomal phenotypes in the PEX11-A and PEX11-D strains expressing constitutively dephosphorylated and phosphorylated forms of Pex11p resemble those of PEX11 gene knock-out and overexpression mutants, although PEX11 transcript and Pex11 protein levels remain unchanged. We demonstrate functional inequality and differences in subcellular localization of the Pex11p forms. Pex11Dp promotes peroxisome fragmentation when reexpressed in cells containing induced peroxisomes. Pex11p translocates between endoplasmic reticulum and peroxisomes in a phosphorylation-dependent manner, whereas Pex11Ap and Pex11Dp are impaired in trafficking and constitutively associated with mature and proliferating peroxisomes, respectively. Overexpression of cyclin-dependent kinase Pho85p results in hyperphosphorylation of Pex11p and peroxisome proliferation. This study provides the first evidence for control of peroxisome dynamics by phosphorylation-dependent regulation of a peroxin.

| S-EPMC2825462 | biostudies-literature

Contribution of ERMES subunits to mature peroxisome abundance.

Project description:Eukaryotic organelles share different components and establish physical contacts to communicate throughout the cell. One of the best-recognized examples of such interplay is the metabolic cooperation and crosstalk between mitochondria and peroxisomes, both organelles being functionally and physically connected and linked to the endoplasmic reticulum (ER). In Saccharomyces cerevisiae, mitochondria are linked to the ER by the ERMES complex that facilitates inter-organelle calcium and phospholipid exchanges. Recently, peroxisome-mitochondria contact sites (PerMit) have been reported and among Permit tethers, one component of the ERMES complex (Mdm34) was shown to interact with the peroxin Pex11, suggesting that the ERMES complex or part of it may be involved in two membrane contact sites (ER-mitochondria and peroxisome- mitochondria). This opens the possibility of exchanges between these three membrane compartments. Here, we investigated in details the role of each ERMES subunit on peroxisome abundance. First, we confirmed previous studies from other groups showing that absence of Mdm10 or Mdm12 leads to an increased number of mature peroxisomes. Secondly, we showed that this is not simply due to respiratory function defect, mitochondrial DNA (mtDNA) loss or mitochondrial network alteration. Finally, we present evidence that the contribution of ERMES subunits Mdm10 and Mdm12 to peroxisome number involves two different mechanisms.

| S-EPMC6433259 | biostudies-literature

PEX16: a multifaceted regulator of peroxisome biogenesis.

Project description:Peroxisomes are formed by two distinct pathwaysthe growth and fission of mature peroxisomes and de novo synthesis at the endoplasmic reticulum (ER). While many of the molecular mechanisms underlying these two pathways remain to be elucidated, it is generally accepted that their relative contribution to peroxisome formation may vary depending on the species, cell type and/or physiological status of the organism. One pertinent example of the apparent differences in the regulation of peroxisome biogenesis among evolutionarily diverse species is the involvement of the peroxin PEX16. In Yarrowia lipolytica, for instance, PEX16 is an intraperoxisomal peripheral membrane protein that participates in peroxisomal fission. By contrast, Human PEX16 is an integral membrane protein that is thought to function at the ER during the early stages of de novo peroxisome formation and also recruits peroxisomal membrane proteins directly to mature peroxisomes. Similarly, PEX16 in the plant Arabidopsis thaliana is speculated to be a PMP receptor at the ER and peroxisomes, and is also required for the formation of other ER-derived organelles, such as oil and protein bodies. Here we briefly review the current knowledge of Y. lipolytica, human and A. thaliana PEX16 in the context of our overall understanding of peroxisome biogenesis and the role of the ER in this process in these three divergent species.

| S-EPMC3759792 | biostudies-literature

The p97-UBXD8 complex maintains peroxisome abundance by suppressing pexophagy.

Project description:Peroxisomes are vital organelles involved in key metabolic functions in eukaryotic cells. Their significance is highlighted by peroxisome biogenesis disorders; severe childhood diseases marked by disrupted lipid metabolism. One mechanism regulating peroxisome abundance is through selective ubiquitylation of peroxisomal membrane proteins that triggers peroxisome degradation via selective autophagy (pexophagy). However, the mechanisms regulating pexophagy remain poorly understood in mammalian cells. Here we show that the evolutionarily conserved AAA-ATPase p97 and its membrane embedded adaptor UBXD8 are essential for maintaining peroxisome abundance. From quantitative proteomic studies we reveal that loss of UBXD8 affects many peroxisomal proteins. We find depletion of UBXD8 results in a loss of peroxisomes in a manner that is independent of the known role of UBXD8 in ER associated degradation (ERAD). Loss of UBXD8 or inhibition of p97 increases peroxisomal turnover through autophagy and can be rescued by depleting key autophagy proteins or overexpressing the deubiquitylating enzyme USP30. Furthermore, we find increased ubiquitylation of the peroxisomal membrane protein PMP70 in cells lacking UBXD8 or p97. Collectively, our findings identify a new role for the p97-UBXD8 complex in regulating peroxisome abundance by suppressing pexophagy.

| S-EPMC11463529 | biostudies-literature

Deubiquitinating enzyme USP30 maintains basal peroxisome abundance by regulating pexophagy.

Project description:The regulation of organelle abundance is critical for cell function and survival; however, the mechanisms responsible are not fully understood. In this study, we characterize a role of the deubiquitinating enzyme USP30 in peroxisome maintenance. Peroxisomes are highly dynamic, changing in abundance in response to metabolic stress. In our recent study identifying the role of USP30 in mitophagy, we observed USP30 to be localized to punctate structures resembling peroxisomes. We report here that USP30, best known as a mitophagy regulator, is also necessary for regulating pexophagy, the selective autophagic degradation of peroxisomes. We find that overexpressing USP30 prevents pexophagy during amino acid starvation, and its depletion results in pexophagy induction under basal conditions. We demonstrate that USP30 prevents pexophagy by counteracting the action of the peroxisomal E3 ubiquitin ligase PEX2. Finally, we show that USP30 can rescue the peroxisome loss observed in some disease-causing peroxisome mutations, pointing to a potential therapeutic target.

| S-EPMC6400567 | biostudies-literature

Mitochondrial fission factor (MFF) is a critical regulator of peroxisome maturation.

Project description:Peroxisomes are highly dynamic subcellular compartments with important functions in lipid and ROS metabolism. Impaired peroxisomal function can lead to severe metabolic disorders with developmental defects and neurological abnormalities. Recently, a new group of disorders has been identified, characterised by defects in the membrane dynamics and division of peroxisomes rather than by loss of metabolic functions. However, the contribution of impaired peroxisome plasticity to the pathophysiology of those disorders is not well understood. Mitochondrial fission factor (MFF) is a key component of both the peroxisomal and mitochondrial division machinery. Patients with MFF deficiency present with developmental and neurological abnormalities. Peroxisomes (and mitochondria) in patient fibroblasts are highly elongated as a result of impaired organelle division. The majority of studies into MFF-deficiency have focused on mitochondrial dysfunction, but the contribution of peroxisomal alterations to the pathophysiology is largely unknown. Here, we show that MFF deficiency does not cause alterations to overall peroxisomal biochemical function. However, loss of MFF results in reduced import-competency of the peroxisomal compartment and leads to the accumulation of pre-peroxisomal membrane structures. We show that peroxisomes in MFF-deficient cells display alterations in peroxisomal redox state and intra-peroxisomal pH. Removal of elongated peroxisomes through induction of autophagic processes is not impaired. A mathematical model describing key processes involved in peroxisome dynamics sheds further light into the physical processes disturbed in MFF-deficient cells. The consequences of our findings for the pathophysiology of MFF-deficiency and related disorders with impaired peroxisome plasticity are discussed.

| S-EPMC7262603 | biostudies-literature

Multiple genetic controls on Rhizobium meliloti syrA, a regulator of exopolysaccharide abundance.

Project description:Exopolysaccharides (EPS) are produced by a wide assortment of bacteria including plant pathogens and rhizobial symbionts. Rhizobium meliloti mutants defective in EPS production fail to invade alfalfa nodules. Production of EPS in R. meliloti is likely controlled at several levels. We have characterized a new gene of this regulatory circuit. syrA was identified by its ability to confer mucoid colony morphology and by its ability to suppress the colonial phenotype of an exoD mutant. Here we show that syrA encodes a 9-kD hydrophobic protein that has sequence similarity to two other EPS regulatory proteins: ExoX of Rhizobium NGR234 and R. meliloti, and Psi of R. leguminosarum bv. phaseoli. The syrA transcription start site lies 522 nucleotides upstream of a non-canonical TTG start codon. The syrA promoter region is similar to the promoter region of the nodulation regulatory protein, nodD3. We found that in free-living bacteria, syrA expression is activated by the regulatory locus, syrM, but not by nodD3. In planta, syrM is not required for expression of syrA. Instead, expression of the nitrogen fixation (nifHDKE) genes upstream of syrA plays a role. Specific and distinct sets of genetic controls may operate at different times during nodule invasion.

| S-EPMC1459771 | biostudies-other

Peroxisome proliferator-activated receptor ? coactivator-1? is a central negative regulator of vascular senescence.

Project description:Cellular senescence influences organismal aging and increases predisposition to age-related diseases, in particular cardiovascular disease, a leading cause of death and disability worldwide. Peroxisome proliferator-activated receptor ? coactivator-1? (PGC-1?) is a master regulator of mitochondrial biogenesis and function, oxidative stress, and insulin resistance. Senescence is associated with telomere and mitochondrial dysfunction and oxidative stress, implying a potential causal role of PGC-1? in senescence pathogenesis.We generated a PGC-1?(+/-)/apolipoprotein E(-/-) mouse model and showed that PGC-1? deficiency promotes a vascular senescence phenotype that is associated with increased oxidative stress, mitochondrial abnormalities, and reduced telomerase activity. PGC-1? disruption results in reduced expression of the longevity-related deacetylase sirtuin 1 (SIRT1) and the antioxidant catalase, and increased expression of the senescence marker p53 in aortas. Further, angiotensin II, a major hormonal inducer of vascular senescence, induces prolonged lysine acetylation of PGC-1? and releases the PGC-1?-FoxO1 complex from the SIRT1 promoter, thus reducing SIRT1 expression. The phosphorylation-defective mutant PGC-1? S570A is not acetylated, is constitutively active for forkhead box O1-dependent SIRT1 transcription, and prevents angiotensin II-induced senescence. Acetylation of PGC-1? by angiotensin II interrupts the PGC-1?-forkhead box O1-SIRT1 feed-forward signaling circuit leading to SIRT1 and catalase downregulation and vascular senescence.PGC-1? is a primary negative regulator of vascular senescence. Moreover, the central role of posttranslational modification of PGC-1? in regulating angiotensin II-induced vascular senescence may inform development of novel therapeutic strategies for mitigating age-associated diseases, such as atherosclerosis.

| S-EPMC3663327 | biostudies-literature

A role for Vps1p, actin, and the Myo2p motor in peroxisome abundance and inheritance in Saccharomyces cerevisiae.

Project description:In vivo time-lapse microscopy reveals that the number of peroxisomes in Saccharomyces cerevisiae cells is fairly constant and that a subset of the organelles are targeted and segregated to the bud in a highly ordered, vectorial process. The dynamin-like protein Vps1p controls the number of peroxisomes, since in a vps1Delta mutant only one or two giant peroxisomes remain. Analogous to the function of other dynamin-related proteins, Vps1p may be involved in a membrane fission event that is required for the regulation of peroxisome abundance. We found that efficient segregation of peroxisomes from mother to bud is dependent on the actin cytoskeleton, and active movement of peroxisomes along actin filaments is driven by the class V myosin motor protein, Myo2p: (a) peroxisomal dynamics always paralleled the polarity of the actin cytoskeleton, (b) double labeling of peroxisomes and actin cables revealed a close association between both, (c) depolymerization of the actin cytoskeleton abolished all peroxisomal movements, and (d) in cells containing thermosensitive alleles of MYO2, all peroxisome movement immediately stopped at the nonpermissive temperature. In addition, time-lapse videos showing peroxisome movement in wild-type and vps1Delta cells suggest the existence of various levels of control involved in the partitioning of peroxisomes.

| S-EPMC2150915 | biostudies-literature

ANKRD9 is a metabolically-controlled regulator of IMPDH2 abundance and macro-assembly.

Project description:Members of a large family of Ankyrin Repeat Domain (ANKRD) proteins regulate numerous cellular processes by binding to specific protein targets and modulating their activity, stability, and other properties. The same ANKRD protein may interact with different targets and regulate distinct cellular pathways. The mechanisms responsible for switches in the ANKRDs' behavior are often unknown. We show that cells' metabolic state can markedly alter interactions of an ANKRD protein with its target and the functional outcomes of this interaction. ANKRD9 facilitates degradation of inosine monophosphate dehydrogenase 2 (IMPDH2), the rate-limiting enzyme in GTP biosynthesis. Under basal conditions ANKRD9 is largely segregated from the cytosolic IMPDH2 in vesicle-like structures. Upon nutrient limitation, ANKRD9 loses its vesicular pattern and assembles with IMPDH2 into rodlike filaments, in which IMPDH2 is stable. Inhibition of IMPDH2 activity with ribavirin favors ANKRD9 binding to IMPDH2 rods. The formation of ANKRD9/IMPDH2 rods is reversed by guanosine, which restores ANKRD9 associations with the vesicle-like structures. The conserved Cys109Cys110 motif in ANKRD9 is required for the vesicle-to-rods transition as well as binding and regulation of IMPDH2. Oppositely to overexpression, ANKRD9 knockdown increases IMPDH2 levels and prevents formation of IMPDH2 rods upon nutrient limitation. Taken together, the results suggest that a guanosine-dependent metabolic switch determines the mode of ANKRD9 action toward IMPDH2.

| S-EPMC6768640 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data