Oligodendroglial impact on axonal function and survival – a hypothesis

Kassmann, Celia M.; Nave, Klaus‐Armin

doi:10.1097/wco.0b013e328300c71f

Cited by 52 publications

(35 citation statements)

References 55 publications

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“…Because VLCFAs are metabolized in peroxisomes via ␤ -oxidation, myelinating glial cells in ALDpatients accumulate VLCFA, which causes dysmyelination but also infl ammatory-induced demyelination. The latter may be caused by the failure to degrade arachidonic acidderived eicosanoids ( 72,73 ). Peroxisome biogenesis disorders of Zellweger syndrome occur when any one of 12 peroxins involved in the import of peroxisomal proteins is mutated [for a recent review, see ( 74 )].…”

Section: Fatty Acid and Plasmalogen Disordersmentioning

confidence: 99%

Lipid metabolism in myelinating glial cells: lessons from human inherited disorders and mouse models

Chrast

Saher

Nave

et al. 2011

Journal of Lipid Research

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253

244

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Section: Fatty Acid and Plasmalogen Disordersmentioning

confidence: 99%

Lipid metabolism in myelinating glial cells: lessons from human inherited disorders and mouse models

Chrast

Saher

Nave

et al. 2011

Journal of Lipid Research

Self Cite

253

244

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“…However, it is known that the inability to maintain peroxisome numbers is linked to various neurodegenerative and developmental disorders such as X-linked adrenoleukodystrophy, and Krabbe disease (Ribeiro et al, 2012;Singh et al, 2009). In particular, in some leukodystrophies, the loss of peroxisomes during neuroinflammation is thought to exacerbate the cellular inflammation, eventually leading to cell death (Kassmann and Nave, 2008).…”

Section: Introductionmentioning

confidence: 99%

NBR1 acts as an autophagy receptor for peroxisomes

Deosaran

Larsen

Hua

et al. 2012

Journal of Cell Science

295

359

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SummarySelective macro-autophagy is an intracellular process by which large cytoplasmic materials are selectively sequestered and degraded in the lysosomes. Substrate selection is mediated by ubiquitylation and recruitment of ubiquitin-binding autophagic receptors such as p62, NBR1, NDP52 and Optineurin. Although it has been shown that these receptors act cooperatively to target some types of substrates to nascent autophagosomes, their precise roles are not well understood. We examined selective autophagic degradation of peroxisomes (pexophagy), and found that NBR1 is necessary and sufficient for pexophagy. Mutagenesis studies of NBR1 showed that the amphipathic a-helical J domain, the ubiquitin-associated (UBA) domain, the LC3-interacting region and the coiled-coil domain are necessary to mediate pexophagy. Strikingly, substrate selectivity is partly achieved by NBR1 itself by coincident binding of the J and UBA domains to peroxisomes. Although p62 is not required when NBR1 is in excess, its binding to NBR1 increases the efficiency of NBR1-mediated pexophagy. Together, these results suggest that NBR1 is the specific autophagy receptor for pexophagy.

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“…[12][13][14][15][16] These results indicate that peroxisomal fatty acid β-oxidation in glial cells is indispensable for the maintenance of myelin. In the central nervous system (CNS), ABCD1 is highly expressed in astrocytes and microglia in the subcortical and cerebellar white matter.…”

mentioning

confidence: 70%

Very Long Chain Fatty Acid β-Oxidation in Astrocytes: Contribution of the ABCD1-Dependent and -Independent Pathways

Morita

Shinbo

Asahi

et al. 2012

Biological & Pharmaceutical Bulletin

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Very long chain fatty acid (VLCFA) metabolism in astrocytes is important for the maintenance of myelin structure in central nervous system. To analyze the contribution of the ABCD1-dependent and -independent pathways to VLCFA metabolism in astrocytes, we prepared human glioblastoma U87 cells with a silencing of ABCD1 and primary astrocytes from abcd1-deficient mice, and measured fatty acid β-oxidation in the presence or absence of a potent inhibitor of carnitine palmitoyltransferase I, 2-[5-(4-chlorophenyl)pentyl]oxirane-2-carboxylate (POCA). In U87 cells, C24:0 β-oxidation was decreased to ca. 70% of the control in the presence of POCA, and the activity was further decreased to ca. 20% by the silencing of ABCD1. In mouse primary astrocytes, C24:0 β-oxidation was also decreased to ca. 70% of the control in the presence of POCA. The C24:0 β-oxidation in Abcd1-deficient primary astrocytes was ca. 60% of the wild-type cells and the activity was further decreased to ca. 25% in the presence of POCA. Compared to human skin fibroblasts, in which VLCFA β-oxidation is not significantly inhibited by POCA, approximately one-third of the overall VLCFA β-oxidation was inhibited in both types of astrocytic cells. These results suggest that VLCFA is indeed β-oxidized in ABCD1-dependent pathway, but the ABCD1-independent peroxisomal and mitochondrial β-oxidation pathways significantly contribute to VLCFA β-oxidation in astrocytic cells.Key words very long chain fatty acid β-oxidation; astrocyte; ABCD1; peroxisome; mitochondria Peroxisomes are single membrane organelles that are present in almost all eukaryotic cells. The peroxisomes are involved in a variety of metabolic processes, including the β-oxidation of fatty acids, especially very long chain fatty acids (VLCFA, >C22), and the synthesis of ether phospholipids and bile acids in mammals.1) Transport of substrates for fatty acid β-oxidation across the peroxisomal membrane is an essential step in this metabolism. Peroxisomal ATP-binding cassette (ABC) proteins have been implicated in this transport.To date, three ABC proteins, classified into "subfamily D," have been identified in mammalian peroxisomes. These are adrenoleukodystrophy protein (ALDP/ABCD1),2) ALDP-related protein (ALDRP/ABCD2) 3) and a 70-kDa peroxisomal membrane protein (PMP70/ABCD3). 4) Dysfunction of ABCD1 causes the human genetic disorder X-linked adrenoleukodystrophy (X-ALD) characterized by an accumulation of VLCFA because of the impaired peroxisomal β-oxidation of VLCFA.5) VLCFA β-oxidation in X-ALD patient fibroblasts was restored by the expression of ABCD1. Likewise, the expression of ABCD2, which has a high sequence similarity to ABCD1, also restored VLCFA β-oxidation in X-ALD fibro blasts.6) In analogy to the role of Pxa1p/Pxa2p, 7) yeast peroxisomal half-ABC transporters, which is involved in the transport of acyl-CoA, ABCD1 and ABCD2 are thought to be involved in the metabolic transport of VLCFA-CoA. 8,9) ABCD3 is suggested to be involved in the metabolic transport of long chain fatty acids (LCFA)...

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Oligodendroglial impact on axonal function and survival – a hypothesis

Abstract: Collectively, experimental and pathological findings point to a primary role of myelinating glia in long-term axonal support and suggest that defects of lipid metabolism in oligodendrocytes contribute to inflammatory myelin diseases.

Cited by 52 publications

References 55 publications

Lipid metabolism in myelinating glial cells: lessons from human inherited disorders and mouse models

Lipid metabolism in myelinating glial cells: lessons from human inherited disorders and mouse models

NBR1 acts as an autophagy receptor for peroxisomes

Very Long Chain Fatty Acid β-Oxidation in Astrocytes: Contribution of the ABCD1-Dependent and -Independent Pathways

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