Decreased synthesis and inefficient mitochondrial import of hsp60 in a patient with a mitochondrial encephalomyopathy

A Huckriede, E Agsteribbe

    Research output: Contribution to journalArticleAcademicpeer-review

    43 Citations (Scopus)

    Abstract

    In a recent paper (Agsteribbe et al. (1993) Biochem. Biophys. Res. Commun. 193, 146-154) we suggested deficiency of heat shock protein 60 (hsp60) as the possible cause of a systemic mitochondrial encephalomyopathy with multiple deficiency of mitochondrial enzymes. In this paper we present new data which strongly support this hypothesis. Hsp60 deficiency appeared to be not a common side effect of impaired mitochondrial metabolism as eight out of ten fibroblast cultures from patients with systemic mitochondrial myopathy contained normal quantities of the protein. The low steady state amount of hsp60 in the fibroblasts of our patient is caused by decreased synthesis of the protein and not by its enhanced degradation indicating that the hsp60 deficiency is indeed a primary defect. Processing of hsp60 but not of other mitochondrial proteins is markedly retarded in the patient cells. Other functional properties of the patient hsp60 like the assembly of hsp60 monomers to the native 14mer complex and the affinity of this complex to denatured protein are not impaired. Our results underline that a primary defect in hsp60 synthesis and/or processing causing a low steady state amount of hsp60 is the molecular basis of this mitochondrial disorder. The presented data provide for the first time substantial evidence that deficiency of a heat shock protein can give rise to pathological conditions in man.

    Original languageEnglish
    Pages (from-to)200-206
    Number of pages7
    JournalBiochimica et biophysica acta-Molecular basis of disease
    Volume1227
    Issue number3
    DOIs
    Publication statusPublished - 29-Nov-1994

    Keywords

    • MITOCHONDRIAL TRANSPORT
    • HEAT SHOCK PROTEIN 60
    • MITOCHONDRIAL ENCEPHALOMYOPATHY
    • YEAST MITOCHONDRIA
    • PROTEIN
    • DISEASE
    • CHAIN
    • DNA
    • PURIFICATION
    • FIBROBLASTS
    • MYOPATHIES
    • DIAGNOSIS
    • DELETIONS

    Cite this