Extended polyglutamine repeats trigger a feedback loop involving the mitochondrial complex III, the proteasome and huntingtin aggregates.

Extended polyglutamine repeats trigger a feedback loop involving the mitochondrial complex III, the proteasome and huntingtin aggregates. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Extended polyglutamine repeats trigger a feedback loop involving the mitochondrial complex III, the proteasome and huntingtin aggregates. Abstract Text:

Hirokazu Fukui,Carlos T Moraes,

Mitochondrial abnormalities represent a major cytopathology in Huntington's disease (HD), a fatal neurodegenerative disease caused by CAG repeat expansions in the gene encoding huntingtin (Htt). In the present study, we investigated whether defects in the mitochondrial respiratory function are consequences of the expression of mutant Htt or they promote the formation of Htt aggregates. To take advantage of existing mitochondrial DNA mutants, we developed human osteosarcoma 143B cells expressing mutant Htt in an inducible manner and found that cells expressing mutant Htt but not wild-type Htt exhibited a reduced activity of complex III and an increased activity of complex IV. Conversely, pharmacological treatments that inhibited complex III activity significantly promoted the formation of Htt aggregates. This complex III-mediated modulation of Htt aggregates was also observed in a neuronal progenitor RN33B cell line transduced by lentivirus carrying mutant Htt. This effect of complex III inhibition on the Htt aggregates appeared to be mediated by the inhibition of proteasome activity, but not by ATP depletion or production of reactive oxygen species. Accordingly, complex III mutant cells also showed decreased proteasome activity. These results suggest the presence of a feedback system connecting the mitochondrial respiratory complex III and the production of Htt aggregates. Our results suggest that therapeutic interventions targeting complex III and/or proteasome could ameliorate the progress of HD.

Extended polyglutamine repeats trigger a feedback loop involving the mitochondrial complex III, the proteasome and huntingtin aggregates. Publishing Authors By Initials

H Fukui,CT Moraes,

For similar genetic processes: mutagenesis: dna repeat expansion: trinucleotide repeat expansion research abstracts see: genetic processes: mutagenesis: dna repeat expansion: trinucleotide repeat expansion research

PUBMED ID PMID:

MEDLINE DATE:

Extended polyglutamine repeats trigger a feedback loop involving the mitochondrial complex III, the proteasome and huntingtin aggregates. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Human molecular genetics

VOLUME: 16

Page Numbers: 783-97

Journal Abbreviation:

ISSN: 0964-6906

DAY: 13

MONTH: 03

YEAR: 2007

Extended polyglutamine repeats trigger a feedback loop involving the mitochondrial complex III, the proteasome and huntingtin aggregates. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9208958

Extended polyglutamine repeats trigger a feedback loop involving the mitochondrial complex III, the proteasome and huntingtin aggregates. Keywords Mesh Terms:

KEYWORDS: Trinucleotide Repeat Expansion

MESH TERMS: metabolism

Chemical & Substance for Abstract: Extended polyglutamine repeats trigger a feedback loop involving the mitochondrial complex III, the proteasome and huntingtin aggregates. Information

Substance Name: Proteasome Endopeptidase Complex

Registry Number: EC 3.4.25.1

Grant and Affiliation Information for Extended polyglutamine repeats trigger a feedback loop involving the mitochondrial complex III, the proteasome and huntingtin aggregates.

AFFILIATION: Neuroscience Program, University of Miami Miller School of Medicine, Miami, FL 33136, USA.

Country: England

AGENCY: United States NINDS

GRANT: R01-NS41777

ACRONYM: NS

MEDLINETA: Hum Mol Genet

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Extended polyglutamine repeats trigger a feedback loop involving the mitochondrial complex III, the proteasome and huntingtin aggregates Related Publications

• Carbamazepine protects the CNS of Wistar rats against the central effects of scorpion envenomation.
• Culture of transgenic Drosophila melanogaster Schneider 2 cells in serum-free media based on TC100 basal medium.
• Cytochrome c oxidase deficiency in neurons decreases both oxidative stress and amyloid formation in a mouse model of Alzheimer's disease.
• Extended polyglutamine repeats trigger a feedback loop involving the mitochondrial complex III, the proteasome and huntingtin aggregates.
• In field-grown coffee trees source-sink manipulation alters photosynthetic rates, independently of carbon metabolism, via alterations in stomatal function.
• Inter- and intraspecific variation in defensive compounds produced by five neotropical stink bug species (Hemiptera: Pentatomidae).
• Intraarticular synovial hemangioma of the knee: an unusual cause of chronic pain in a sportsman.
• Modulating mtDNA heteroplasmy by mitochondria-targeted restriction endonucleases in a 'differential multiple cleavage-site' model.
• Ninjurin 1 asp110ala single nucleotide polymorphism is associated with protection in leprosy nerve damage.
• PGC-1alpha/beta upregulation is associated with improved oxidative phosphorylation in cells harboring nonsense mtDNA mutations.
• Pathophysiology and fate of hepatocytes in a mouse model of mitochondrial hepatopathies.
• Reliability of two methods for measurement of alveolar bone level in children.
• Role of cytochrome C in apoptosis: increased sensitivity to tumor necrosis factor alpha is associated with respiratory defects but not with lack of cytochrome C release.
• Stratus optical coherence tomography findings in patients with retinopathy of prematurity.
• Synthesis and cytotoxic activity of some 3-benzyl-5-arylidenefuran-2(5H)-ones.
• Transcriptional co-expression and co-regulation of genes coding for components of the oxidative phosphorylation system.
• Transmitochondrial technology in animal cells.
• Traumatic intrusion of maxillary permanent incisors into the nasal cavity: report of a case.
• Ulceration of striae distensae in a patient with systemic lupus erythematosus.
• [Brazilian guidelines proposal for screening and treatment of retinopathy of prematurity (ROP).]
• [Collection and analysis of basic data on vaccination programs]
• [Electroretinographic study of chromatic vision]
• [Haemodynamic effects of intoxication with bupivacaine and enantiomeric excess mixture: experimental study in swine.]
• [Household solid waste bagging and collection and their health implications for children living in outlying urban settlements in Salvador, Bahia State, Brazil.]
• [In Process Citation]
• [Left thoracotomy for reoperations in myocardium revascularization.]
• [Method of obtaining data on morbidity.]
• [Operationalizing the cross-cultural adaptation of epidemiological measurement instruments]
• [Retinal central vein occlusion in remission of Crohn's disease: case report.]
• [Sexual activity after myocardial infarction: taboo or lack of knowledge?]