Functional characterisation of ganglioside-induced differentiation-associated protein 1 as a glutathione transferase

Shield, Alison; Murray, Tracy P.; Board, Philip G.

doi:10.1016/j.bbrc.2006.06.189

Cited by 61 publications

(71 citation statements)

References 35 publications

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“…Phylogenetic and structural analyses suggest that GDAP1 belongs to a subfamily of glutathione-S-transferases (GSTs). However, no functional GST activity associated to this protein has been found so far [ 75 ]. Unlike other proteins involved in mitochondrial fusion and fi ssion containing GTPase and dynamin domains, GDAP1 sequence analysis does not suggest any involvement in mitochondrial dynamics.…”

Section: Mitochondrial Fissionmentioning

confidence: 89%

Mitochondrial Dynamics and Neurodegeneration

Mourier

2016

Mitochondrial Dysfunction in Neurodegenerative Disorders

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In vivo, mitochondria display a high degree of connectivity and mobility. Within the cell, mitochondrial fusion and fi ssion machineries tightly control the dynamics and distribution of the mitochondrial network. Due to their key energetic role, the localization of mitochondria at intracellular sites of high-energy demand is crucial to maintain cell energy metabolism. Neurons are metabolically active cells with high-energy demands at locations distant from the cell body (see Chaps. 8 and 9 ). Consequently, they are particularly dependent on mitochondrial distribution and function. Accordingly, new evidence identifi es defective mitochondrial dynamics as a central pathological event underpinning a number of early and late-onset neurodegenerative disorders. Mutations in genes encoding proteins playing central roles in mitochondrial dynamics and functions have been identifi ed in patients with peripheral neuropathies such as Charcot-Marie-Tooth (CMT) and dominant inherited optic atrophy. Moreover, defects of mitochondrial dynamics have recently been associated with common neurodegenerative diseases such as Parkinson's, Alzheimer's, and Huntington's diseases. Understanding the regulation of mitochondrial dynamics in neurons may open new avenues for the development of therapies in neurodegenerative diseases.

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Section: Mitochondrial Fissionmentioning

confidence: 89%

Mitochondrial Dynamics and Neurodegeneration

Mourier

2016

Mitochondrial Dysfunction in Neurodegenerative Disorders

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“…However, GDAP1 has appeared recently in evolution in multicellular organisms, especially in vertebrates (14), and it is expressed mainly in the nervous system (11). Furthermore, GDAP1 defects cause a peripheral neuropathy (11)(12)(13)33), and the affected neurons are post-mitotic non-dividing cells.…”

Section: Gdap1 Complements the Fis1⌬ Phenotype In S Cerevisiaementioning

confidence: 99%

“…For this reason, we believe that complementation failure of GDAP1 mutants could be the consequence of an abnormal gain-of-function mechanism that might affect spindle formation and other associated phenotypes. This mechanism would be mediated by the ␣-loop domain, for which no structural and biological information has been defined yet (14).…”

Section: Gdap1 Complements the Fis1⌬ Phenotype In S Cerevisiaementioning

confidence: 99%

“…Results show that the missense mutations could bind TUBB and that this interaction was increased in all of them. C, a ␤-galactosidase lift assay was performed to test the interaction between GDAP1 (first lane) and the following GDAP1 domains: GST-N terminus (Nt; amino acids 24 -105), ␣-loop (amino acids 106 -152), GST-C terminus (Ct; amino acids 153-309), and the TMD (amino acids 310 -358) (14). TUBB specifically interacted with the ␣-loop domain.…”

Section: Volume 286 • Number 42 • October 21 2011mentioning

confidence: 99%

“…It is located in the mitochondrial outer membrane and is expressed mainly in neurons (9 -11). Although GDAP1 sequence has a high level of similarity to glutathione S-transferase (GST) (12,13), no GST activity has been reported previously (10,14). Mutations in GDAP1 are the cause of the Charcot-Marie-Tooth (CMT) 2 disease: autosomal recessive demyelinating CMT4A (15) autosomal recessive axonal ARCMT2K or dominant axonal CMT2K.…”

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Charcot-Marie-Tooth-related Gene GDAP1 Complements Cell Cycle Delay at G2/M Phase in Saccharomyces cerevisiae fis1 Gene-defective Cells

Estela

Pla‐Martín

Sánchez-Piris

et al. 2011

Journal of Biological Chemistry

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Mutations in the GDAP1 gene are responsible of the CharcotMarie-Tooth CMT4A, ARCMT2K, and CMT2K variants. GDAP1 is a mitochondrial outer membrane protein that has been related to the fission pathway of the mitochondrial network dynamics. As mitochondrial dynamics is a conserved process, we reasoned that expressing GDAP1 in Saccharomyces cerevisiae strains defective for genes involved in mitochondrial fission or fusion could increase our knowledge of GDAP1 function. We discovered a consistent relation between Fis1p and the cell cycle because fis1⌬ cells showed G 2 /M delay during cell cycle progression. The fis1⌬ phenotype, which includes cell cycle delay, was fully rescued by GDAP1. By contrast, clinical missense mutations rescued the fis1⌬ phenotype except for the cell cycle delay. In addition, both Fis1p and human GDAP1 interacted with ␤-tubulins Tub2p and TUBB, respectively. A defect in the fis1 gene may induce abnormal location of mitochondria during budding mitosis, causing the cell cycle delay at G 2 /M due to its anomalous interaction with microtubules from the mitotic spindle. In the case of neurons harboring defects in GDAP1, the interaction between mitochondria and the microtubule cytoskeleton would be altered, which might affect mitochondrial axonal transport and movement within the cell and may explain the pathophysiology of the GDAP1-related Charcot-Marie-Tooth disease.

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Functional Genomics of the Human Glutathione Transferases

Board

2012

Encyclopedia of Drug Metabolism and Interactions

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The glutathione transferase (GST) super family of enzymes catalyze the conjugation of glutathione (GSH) to a wide range of exogenous and endogenous compounds. In addition to catalytic reactions, the GSTs also modulate several cell signaling kinases and ion channels such as Jun N‐terminal kinase and ryanodine receptors via protein /protein interactions. Pharmacogenetic studies have identified variations in drug response and susceptibility to cancer and other disorders associated with variant GST isoforms. In humans, the cytosolic GSTs have been subdivided into seven distinct classes termed Alpha, Mu, Pi, Theta, Sigma, Zeta , and Omega and there are multiple genes in some classes. So far, 48 allelic variants that cause amino acid substitutions have been documented, and in many cases, the variant proteins have been functionally and structurally characterized. Some polymorphisms in promoter regions have been shown to affect the level of GST expression in vitro and in vivo , and this area requires further investigation. Although the various members of the GST superfamily are characterized by striking differences in the reactions they catalyze and their substrate specificities, they share a similar structural fold. Representative structures of all the human GST classes have been determined by X‐ray crystallography.

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Functional characterisation of ganglioside-induced differentiation-associated protein 1 as a glutathione transferase

Cited by 61 publications

References 35 publications

Mitochondrial Dynamics and Neurodegeneration

Mitochondrial Dynamics and Neurodegeneration

Charcot-Marie-Tooth-related Gene GDAP1 Complements Cell Cycle Delay at G2/M Phase in Saccharomyces cerevisiae fis1 Gene-defective Cells

Functional Genomics of the Human Glutathione Transferases

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