Molecular genetics of peroxisomal disorders

Moser, Hugo W.

doi:10.2741/moser

Cited by 29 publications

(6 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Some special biochemical reactions, such as penicillin biosynthesis in Penicillium species, methanol utilization in yeasts and photorespiration in plants, also rely on peroxisomes [3], [4], [5]. The significance of peroxisomes in humans was demonstrated by diseases due to peroxisomal biogenesis disorders (PBDs), such as the Zellweger syndrome, the neonatal adrenoleukodystrophy, and the infantile Refsum’s disease [6].…”

Section: Introductionmentioning

confidence: 99%

PTS1 Peroxisomal Import Pathway Plays Shared and Distinct Roles to PTS2 Pathway in Development and Pathogenicity of Magnaporthe oryzae

et al. 2013

View full text Add to dashboard Cite

Peroxisomes participate in various important metabolisms and are required in pathogenicity of fungal plant pathogens. Peroxisomal matrix proteins are imported from cytoplasm into peroxisomes through peroxisomal targeting signal 1 (PTS1) or peroxisomal targeting signal 2 (PTS2) import pathway. PEX5 and PEX7 genes participate in the two pathways respectively. The involvement of PEX7 mediated PTS2 import pathway in fungal pathogenicity has been documented, while that of PTS1 remains unclear. Through null mutant analysis of MoPEX5, the PEX5 homolog in Magnaporthe oryzae, we report the crucial roles of PTS1 pathway in the development and host infection in the rice blast fungus, and compared with those of PTS2. We found that MoPEX5 disruption specifically blocked the PTS1 pathway. Δmopex5 was unable to use lipids as sole carbon source and lost pathogenicity completely. Similar as Δmopex7, Δmopex5 exhibited significant reduction in lipid utilization and mobilization, appressorial turgor genesis and H2O2 resistance. Additionally, Δmopex5 presented some distinct defects which were undetected in Δmopex7 in vegetative growth, conidial morphogenesis, appressorial morphogenesis and melanization. The results indicated that the PTS1 peroxisomal import pathway, in addition to PTS2, is required for fungal development and pathogenicity of the rice blast fungus, and also, as a main peroxisomal import pathway, played a more predominant role than PTS2.

show abstract

Section: Introductionmentioning

confidence: 99%

PTS1 Peroxisomal Import Pathway Plays Shared and Distinct Roles to PTS2 Pathway in Development and Pathogenicity of Magnaporthe oryzae

et al. 2013

View full text Add to dashboard Cite

show abstract

“…To further explore previously unknown EL functions, we generated an EL-deficient mouse model by targeted deletion of DAPAT (3,4). EL-deficient mice show severe phenotypes including development of cataract, various abnormalities of the central nervous system (CNS) (5) and arrest of spermatogenesis (6), changes that are reminiscent of rhizomelic chondrodysplasia punctata (RCDP) types 2 and 3, human peroxisomal disorders distinguished by isolated genetic defects in EL biosynthesis (7,8). Patients with severe RCDP show magnetic resonance imaging abnormalities the severity of which correlates with the clinical appearance and the level of PLs (7–9).…”

Section: Introductionmentioning

confidence: 99%

“…EL-deficient mice show severe phenotypes including development of cataract, various abnormalities of the central nervous system (CNS) (5) and arrest of spermatogenesis (6), changes that are reminiscent of rhizomelic chondrodysplasia punctata (RCDP) types 2 and 3, human peroxisomal disorders distinguished by isolated genetic defects in EL biosynthesis (7,8). Patients with severe RCDP show magnetic resonance imaging abnormalities the severity of which correlates with the clinical appearance and the level of PLs (7–9). Both RCDP patients and mice with targeted deletion of the DAPAT gene share phenotypes, such as growth retardation, bilateral cataract, motor impairment and defects in myelination (4,5), suggesting these mice to be a useful model system of RCDP.…”

Section: Introductionmentioning

confidence: 99%

Impaired neurotransmission in ether lipid-deficient nerve terminals

Brodde

Teigler

Brügger

et al. 2012

Human Molecular Genetics

View full text Add to dashboard Cite

Isolated defects of ether lipid (EL) biosynthesis in humans cause rhizomelic chondrodysplasia punctata type 2 and type 3, serious peroxisomal disorders. Using a previously described mouse model [Rodemer, C., Thai, T.P., Brugger, B., Kaercher, T., Werner, H., Nave, K.A., Wieland, F., Gorgas, K., and Just, W.W. (2003) Inactivation of ether lipid biosynthesis causes male infertility, defects in eye development and optic nerve hypoplasia in mice. Hum. Mol. Genet., 12, 1881-1895], we investigated the effect of EL deficiency in isolated murine nerve terminals (synaptosomes) on the pre-synaptic release of the neurotransmitters (NTs) glutamate and acetylcholine. Both Ca(2+)-dependent exocytosis and Ca(2+)-independent efflux of the transmitters were affected. EL-deficient synaptosomes respire at a reduced rate and exhibit a lowered adenosin-5'-triphosphate/adenosine diphosphate (ATP/ADP) ratio. Consequently, ATP-driven processes, such as synaptic vesicle cycling and maintenance of Na(+), K(+) and Ca(2+) homeostasis, might be disturbed. Analyzing reactive oxygen species in EL-deficient neural and non-neural tissues revealed that plasmalogens (PLs), the most abundant EL species in mammalian central nervous system, considerably contribute to the generation of the lipid peroxidation product malondialdehyde. Although EL-deficient tissue contains less lipid peroxidation products, fibroblasts lacking ELs are more susceptible to induced oxidative stress. In summary, these results suggest that due to the reduced energy state of EL-deficient tissue, the Ca(2+)-independent efflux of NTs increases while the Ca(2+)-dependent release declines. Furthermore, lack of PLs is mainly compensated for by an increase in the concentration of phosphatidylethanolamine and results in a significantly lowered level of lipid peroxidation products in the brain cortex and cerebellum.

show abstract

“…Peroxisomes (Po) are ubiquitous organelles contributing to various catabolic as well as anabolic pathways, for example, β-oxidation of long and very long-chain fatty acids, detoxification of reactive oxygen species, synthesis of plasmalogens or bile acids. Their biological significance is well-documented by the existence of more than 15 inherited peroxisomal disorders, which are often lethal for the affected individuals. , Among the different tissues investigated so far, liver and kidney house the highest concentrations of these organelles. Accordingly, the proteome of hepatic and renal Po is the most intensively elaborated up to now. − Commonly, all these studies focused on the peroxisomal fraction enriched at 37 000 g in the classic light mitochondrial fraction first described by Baudhuin et al As revealed, however, by the activities of peroxisomal marker enzymes distributed to the remaining fractions of this classical scheme of differential centrifugation, considerable amounts of Po also sediment at lower centrifugal forces (∼23%), and are not represented in common studies.…”

Section: Introductionmentioning

confidence: 99%

“…Their biological significance is well-documented by the existence of more than 15 inherited peroxisomal disorders, which are often lethal for the affected individuals. 1,2 Among the different tissues investigated so far, liver and kidney house the highest concentrations of these organelles. Accordingly, the proteome of hepatic and renal Po is the most intensively elaborated up to now.…”

Section: Introductionmentioning

confidence: 99%

Peroxisomes from the Heavy Mitochondrial Fraction: Isolation by Zonal Free Flow Electrophoresis and Quantitative Mass Spectrometrical Characterization

Islinger

Loos

et al. 2009

J. Proteome Res.

View full text Add to dashboard Cite

Peroxisomes are a heterogeneous group of organelles fulfilling reactions in a variety of metabolic pathways. To investigate if functionally different subpopulations can be found within a single tissue, peroxisomes from the heavy mitochondrial fraction (HM-Po) of the rat liver were isolated and compared to "classic" peroxisomes from the light mitochondrial fraction (LM-Po) using iTRAQ tandem mass spectrometry. Peroxisomes represent only a minor although significant proportion of the heavy mitochondrial fraction (2700g(max)) precluding a straightforward isolation by standard protocols. Thus, a new fractionation scheme suitable for a subsequent mass spectrometrical analysis was developed using a combination of centrifugation techniques and zonal free flow electrophoresis. On the basis of the iTRAQ-measurement, a variation of the peroxisomal protein pattern between both fractions could be determined and further confirmed by immunoblotting and enzyme activity assays for selected proteins: whereas peroxisomes from the light mitochondrial fraction contain high amounts of beta-oxidation enzymes, peroxisomes from the heavy mitochondrial fraction were dominated by enzymes fulfilling other functions. Among other findings, HM-Po was characterized by a high abundance of D-amino acid oxidase. This observation can be mirrored at the ultrastructural level, where tissue sections of liver peroxisomes show a heterogeneous staining for the enzymes activity, when visualized by the cerium technique.

show abstract

Molecular genetics of peroxisomal disorders

Cited by 29 publications

References 65 publications

PTS1 Peroxisomal Import Pathway Plays Shared and Distinct Roles to PTS2 Pathway in Development and Pathogenicity of Magnaporthe oryzae

PTS1 Peroxisomal Import Pathway Plays Shared and Distinct Roles to PTS2 Pathway in Development and Pathogenicity of Magnaporthe oryzae

Impaired neurotransmission in ether lipid-deficient nerve terminals

Peroxisomes from the Heavy Mitochondrial Fraction: Isolation by Zonal Free Flow Electrophoresis and Quantitative Mass Spectrometrical Characterization

Contact Info

Product

Resources

About