Loss of mortalin function in Parkinson's disease-supporting the mitochondrial pathway of neurodegeneration

Lena F. Burbulla, Rejko Krüger*

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapter


Dysfunctional mitochondria have been early implicated in the neurodegenerative process leading to idiopathic Parkinson's disease (PD) based on biochemical and immunohistochemical findings in affected brain regions of PD patients. The identification of genetic causes of PD during the last decade allowed for the first time to study disease-relevant molecular signaling cascades of neurodegeneration. Based on rare families with autosomal recessively inherited forms of early onset PD, first genes were identified that encode proteins that are critical for the maintenance of mitochondrial function and morphology and therefore contribute to the mitochondrial phenotype of PD. For instance, loss of function mutations in the DJ-1 gene cause impaired mitochondrial respiration with accumulation of free oxygen species, disruption of the mitochondrial energy metabolism and characteristic morphological changes of these organelles. Interestingly, the mitochondrial chaperone protein mortalin was identified as a DJ-1-interacting protein by several groups. Subsequent genetic studies in large cohorts of PD patients revealed first loss of function mutations as risk factors for PD. These disease-associated mortalin variants showed effects on mitochondrial dynamics that paralleled the phenotype observed upon lack of DJ-1 in different in vitro and ex vivo models. These results provided first evidence for a mitochondrial matrix chaperone involved in neuronal cell death in PD and strengthen the relevance of a mitochondrial endophenotype in PD. Therefore, functional studies of mortalin allow to dissect the signaling pathways involved in mitochondrial causes of neurodegeneration in PD and may provide new targets for therapeutic approaches in PD.

Original languageEnglish (US)
Title of host publicationMortalin Biology
Subtitle of host publicationLife, Stress and Death
PublisherSpringer Netherlands
Number of pages19
ISBN (Electronic)9789400730274
ISBN (Print)9400730268, 9789400730267
StatePublished - Apr 1 2012


  • DJ-1
  • Mitochondrial dysfunction
  • Mutations
  • Oxidative stress
  • Parkinson's disease

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology
  • General Medicine


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