Late onset motoneuron disorder caused by mitochondrial Hsp60 chaperone deficiency in mice

Raffaella Magnoni, Johan Palmfeldt, Jane H. Christensen, Majken Sand, Francesca Maltecca, Thomas J. Corydon, Mark West, Giorgio Casari, Peter Bross

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Cells rely on efficient protein quality control systems (PQCs) to maintain proper activity of mitochondrial proteins. As part of this system, the mitochondrial chaperone Hsp60 assists folding of matrix proteins and it is an essential protein in all organisms. Mutations in Hspd1, the gene encoding Hsp60, are associated with two human inherited diseases of the nervous system, a dominantly inherited form of spastic paraplegia (SPG13) and an autosomal recessively inherited white matter disorder termed MitCHAP60 disease. Although the connection between mitochondrial failure and neurodegeneration is well known in many neurodegenerative disorders, such as Huntington's disease, Parkinson's disease, and hereditary spastic paraplegia, the molecular basis of the neurodegeneration associated with these diseases is still ill-defined.Here, we investigate mice heterozygous for a knockout allele of the Hspd1 gene encoding Hsp60. Our results demonstrate that Hspd1 haploinsufficiency is sufficient to cause a late onset and slowly progressive deficit in motor functions in mice. We furthermore emphasize the crucial role of the Hsp60 chaperone in mitochondrial function by showing that the motor phenotype is associated with morphological changes of mitochondria, deficient ATP synthesis, and in particular, a defect in the assembly of the respiratory chain complex III in neuronal tissues. In the current study, we propose that our heterozygous Hsp60 mouse model is a valuable model system for the investigation of the link between mitochondrial dysfunction and neurodegeneration.

Original languageEnglish
Pages (from-to)12-23
Number of pages12
JournalNeurobiology of Disease
Volume54
DOIs
Publication statusPublished - Jun 2013

Fingerprint

Motor Neurons
Hereditary Spastic Paraplegia
Haploinsufficiency
Electron Transport Complex III
Paraplegia
Mitochondrial Proteins
Huntington Disease
Protein Folding
Electron Transport
Nervous System Diseases
Neurodegenerative Diseases
Quality Control
Genes
Parkinson Disease
Mitochondria
Proteins
Adenosine Triphosphate
Alleles
Phenotype
Mutation

Keywords

  • Animal model
  • Heat shock protein
  • Hereditary spastic paraplegia
  • Mitochondrial dysfunction
  • Neurodegenerative disorders

ASJC Scopus subject areas

  • Neurology

Cite this

Magnoni, R., Palmfeldt, J., Christensen, J. H., Sand, M., Maltecca, F., Corydon, T. J., ... Bross, P. (2013). Late onset motoneuron disorder caused by mitochondrial Hsp60 chaperone deficiency in mice. Neurobiology of Disease, 54, 12-23. https://doi.org/10.1016/j.nbd.2013.02.012

Late onset motoneuron disorder caused by mitochondrial Hsp60 chaperone deficiency in mice. / Magnoni, Raffaella; Palmfeldt, Johan; Christensen, Jane H.; Sand, Majken; Maltecca, Francesca; Corydon, Thomas J.; West, Mark; Casari, Giorgio; Bross, Peter.

In: Neurobiology of Disease, Vol. 54, 06.2013, p. 12-23.

Research output: Contribution to journalArticle

Magnoni, R, Palmfeldt, J, Christensen, JH, Sand, M, Maltecca, F, Corydon, TJ, West, M, Casari, G & Bross, P 2013, 'Late onset motoneuron disorder caused by mitochondrial Hsp60 chaperone deficiency in mice', Neurobiology of Disease, vol. 54, pp. 12-23. https://doi.org/10.1016/j.nbd.2013.02.012
Magnoni, Raffaella ; Palmfeldt, Johan ; Christensen, Jane H. ; Sand, Majken ; Maltecca, Francesca ; Corydon, Thomas J. ; West, Mark ; Casari, Giorgio ; Bross, Peter. / Late onset motoneuron disorder caused by mitochondrial Hsp60 chaperone deficiency in mice. In: Neurobiology of Disease. 2013 ; Vol. 54. pp. 12-23.
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