ATP13A2 mutations impair mitochondrial function in fibroblasts from patients with Kufor-Rakeb syndrome

Anne Grünewald, Björn Arns, Philip Seibler, Aleksandar Rakovic, Alexander Münchau, Alfredo Ramirez, Carolyn M. Sue, Christine Klein*

*Corresponding author for this work
    31 Citations (Scopus)

    Abstract

    Mutations in . ATP13A2 cause autosomal-recessive parkinsonism (Kufor-Rakeb syndrome; KRS). Because several other parkinsonism-associated proteins have been connected to mitochondrial function and mitophagy, we studied the impact of endogenous mutations in ATPase type 13A2 (ATP13A2) on mitochondria in fibroblasts from KRS patients compared with controls. In patients, we detected decreased adenosine triphosphate (ATP) synthesis rates, increased mitochondrial DNA levels, a higher frequency of mitochondrial DNA lesions, increased oxygen consumption rates, and increased fragmentation of the mitochondrial network. Importantly, overexpression of wild-type ATP13A2 rescued the respiration phenotype. These findings collectively suggest that ATP13A2 contributes to the maintenance of a healthy mitochondrial pool, supporting the hypothesis that impaired mitochondrial clearance represents an important pathogenic mechanism underlying KRS.

    Original languageEnglish
    JournalNeurobiology of Aging
    Volume33
    Issue number8
    ISSN0197-4580
    DOIs
    Publication statusPublished - 01.08.2012

    Fingerprint

    Dive into the research topics of 'ATP13A2 mutations impair mitochondrial function in fibroblasts from patients with Kufor-Rakeb syndrome'. Together they form a unique fingerprint.

    Cite this