Lysosomal Accumulation of Phospholipids in Mucolipidosis IV
Cultured Fibroblasts

Bach, Gideon; Rj, Desnick

doi:10.1159/000469140

Cited by 9 publications

(4 citation statements)

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“…ML is a collective name for the group of autosomal recessive diseases in which the accumulated substrate is phospholipid (Mancini et al, 2000;Mach, 2002). There are four types of ML, types I-III involve the mis-targeting of lysosomal lipid hydrolases, resulting in inefficient processing of endocytosed lipids (Bach and Desnick, 1988;Bargal and Bach, 1989;Slaugenhaupt, 2002). Type IV (ML IV), however, differs slightly as it is linked to mutations in the proposed ionchannel, mucolipin 1 (MCOLN1), a protein suggested to play a role in lysosomal/endosome function (Bargal and Bach, 1989;Fares and Greenwald, 2001;LaPlante et al, 2004).…”

Section: Mucolipidosis (Ml)mentioning

confidence: 99%

Quality control gone wrong: mitochondria, lysosomal storage disorders and neurodegeneration

Osellame

Duchen

2014

British J Pharmacology

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The eukaryotic cell possesses specialized pathways to turn over and degrade redundant proteins and organelles. Each pathway is unique and responsible for degradation of distinctive cytosolic material. The ubiquitin-proteasome system and autophagy (chaperone-mediated, macro, micro and organelle specific) act synergistically to maintain proteostasis. Defects in this equilibrium can be deleterious at cellular and organism level, giving rise to various disease states. Dysfunction of quality control pathways are implicated in neurodegenerative diseases and appear particularly important in Parkinson's disease and the lysosomal storage disorders. Neurodegeneration resulting from impaired degradation of ubiquitinated proteins and α-synuclein is often accompanied by mitochondrial dysfunction. Mitochondria have evolved to control a diverse number of processes, including cellular energy production, calcium signalling and apoptosis, and like every other organelle within the cell, they must be ‘recycled.’ Failure to do so is potentially lethal as these once indispensible organelles become destructive, leaking reactive oxygen species and activating the intrinsic cell death pathway. This process is paramount in neurons which have an absolute dependence on mitochondrial oxidative phosphorylation as they cannot up-regulate glycolysis. As such, mitochondrial bioenergetic failure can underpin neural death and neurodegenerative disease. In this review, we discuss the links between cellular quality control and neurodegenerative diseases associated with mitochondrial dysfunction, with particular attention to the emerging links between Parkinson's and Gaucher diseases in which defective quality control is a defining factor.

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Section: Mucolipidosis (Ml)mentioning

confidence: 99%

Quality control gone wrong: mitochondria, lysosomal storage disorders and neurodegeneration

Osellame

Duchen

2014

British J Pharmacology

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“…There are four types of ML, three of which (MLII, MLIIIa, and MLIIIC) involve incorrect intracellular targeting of lysosomal lipid hydrolases, resulting in inefficient processing of endocytosed lipids (3)(4)(5). Although the cellular phenotype of type IV (MLIV) is similar to other MLs, MLIV is linked to mutations in the ion channel, mucolipin 1 (TRP-ML1), a member of the TRP family of ion channels (6 -8).…”

Section: Mucolipidosis (Ml)mentioning

confidence: 99%

Mitochondrial Aberrations in Mucolipidosis Type IV

Jennings

Zhu

Rbaibi

et al. 2006

Journal of Biological Chemistry

137

124

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Mucolipidosis type IV is a genetic lysosomal storage disease associated with degenerative processes in the brain, eye, and other tissues. Mucolipidosis type IV results from mutations in the gene MCOLN1, which codes for the TRP family ion channel, mucolipin 1. The connection between lysosomal dysfunction and degenerative processes in mucolipidosis type IV is unclear. Here we report that mucolipidosis type IV and several unrelated lysosomal storage diseases are associated with significant mitochondrial fragmentation and decreased mitochondrial Ca

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“…Other clinical manifestations of MLIV include achloridia and hypergastrinaemia (Schiffmann et al 1998;Lubensky et al 1999). At the cellular level, MLIV is a classic lysosomal storage disease with accumulation, in virtually all tissues and cells, of electron-dense vesicles and membranous inclusions containing phospholipids (Bach & Desnick, 1988;Bargal & Bach, 1989) and gangliosides (Zeigler & Bach, 1986). Proteolysis defects have not been shown in MLIV.…”

Section: Mucolipin 1 and MLIVmentioning

confidence: 99%

TRPpathies

Kiselyov

Soyombo

Muallem

2007

The Journal of Physiology

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Many human diseases are caused by mutations in ion channels. Dissecting the pathogenesis of these 'channelopathies' has yielded important insights into the regulation of vital biological processes by ions and has become a productive tool of modern ion channel biology. One of the best examples of a synergism between the clinical and basic science aspects of a modern biological topic is cystic fibrosis. Not only did the identification of the ion channel mutated in cystic fibrosis pinpoint the root cause of this disease, but it also has significantly advanced our understanding of basic biological processes as diverse as protein folding and epithelial fluid and electrolyte secretion. The list of confirmed 'channelopathies' is growing and several members of the TRP family of ion channels have been implicated in human diseases such as mucolipidosis type IV (MLIV), autosomal dominant polycystic kidney disease (ADPKD), familial focal segmental glomerulosclerosis (FSG), hypomagnesemia with secondary hypocalcaemia (HSH), and several forms of cancer. Analysing pathogenesis of the diseases linked to TRP dysregulation provides an exciting means of identifying novel functions of TRP channels.

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Lysosomal Accumulation of Phospholipids in Mucolipidosis IV Cultured Fibroblasts

Cited by 9 publications

References 0 publications

Quality control gone wrong: mitochondria, lysosomal storage disorders and neurodegeneration

Quality control gone wrong: mitochondria, lysosomal storage disorders and neurodegeneration

Mitochondrial Aberrations in Mucolipidosis Type IV

TRPpathies

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