Nuclear gene defects in mitochondrial disorders

M. Zeviani, P. Corona, L. Nijtmans, V. Tiranti

Research output: Contribution to journalArticle

Abstract

An increasing number of nuclear genes have been associated with abnormalities of oxidative phosphorylation and mitochondrial disorders. The protein products of these genes can be grouped into three categories: structural components of the respiratory chain, factors influencing the structural integrity or the copy number of mitochondrial DNA, and proteins which control the formation, assembly and turnover of the respiratory complexes. Loss-of-function mutations in SURF-1, a gene belonging to the third category, have been associated with Leigh syndrome with cytochrome c oxidase deficiency. Mature Surf-1 protein (Surf-lp) is a 30 kDa hydrophobic polypeptide whose function is still unknown. Using antibodies against human Surflp, we demonstrated that this protein is imported into mitochondria as a larger precursor. The same analysis revealed that no protein is present in cell lines harboring loss-of-function mutations of SURF-1, regardless of their type and position. We also generated several constructs with truncated or partially deleted SURF-1 cDNAs. None of these constructs, expressed into SURF-1 null mutant cells, were able to rescue the COX phenotype, suggesting that different regions of the protein are all essential for function. Finally, experiments based on 2D gel electrophoresis indicated that assembly of COX in SURF-1 null mutants is blocked at an early step, most likely before the incorporation of subunit II in the nascent intermediates composed of subunit I alone or subunit I plus subunit IV.

Original languageEnglish
Pages (from-to)401-408
Number of pages8
JournalItalian Journal of Neurological Sciences
Volume20
Issue number6
Publication statusPublished - 1999

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Mitochondrial Diseases
Genes
Proteins
Cytochrome-c Oxidase Deficiency
Leigh Disease
Null Lymphocytes
Mutation
Mitochondrial Proteins
Oxidative Phosphorylation
Electrophoresis, Gel, Two-Dimensional
Electron Transport
Mitochondrial DNA
Mitochondria
Complementary DNA
Phenotype
Cell Line
Peptides
Antibodies

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Psychiatry and Mental health
  • Dermatology

Cite this

Nuclear gene defects in mitochondrial disorders. / Zeviani, M.; Corona, P.; Nijtmans, L.; Tiranti, V.

In: Italian Journal of Neurological Sciences, Vol. 20, No. 6, 1999, p. 401-408.

Research output: Contribution to journalArticle

Zeviani, M, Corona, P, Nijtmans, L & Tiranti, V 1999, 'Nuclear gene defects in mitochondrial disorders', Italian Journal of Neurological Sciences, vol. 20, no. 6, pp. 401-408.
Zeviani, M. ; Corona, P. ; Nijtmans, L. ; Tiranti, V. / Nuclear gene defects in mitochondrial disorders. In: Italian Journal of Neurological Sciences. 1999 ; Vol. 20, No. 6. pp. 401-408.
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