Contribution of defective mitophagy to the neurodegeneration in DNA repair-deficient disorders

Research output: Contribution to journalJournal articleResearchpeer-review

Morten Scheibye-Knudsen, Evandro Fei Fang, Deborah L. Croteau, Vilhelm A. Bohr

DNA repair is a prerequisite for life as we know it, and defects in DNA repair lead to accelerated aging. Xeroderma pigmentosum group A (XPA) is a classic DNA repair-deficient disorder with patients displaying sun sensitivity and cancer susceptibility. XPA patients also exhibit neurodegeneration, leading to cerebellar atrophy, neuropathy, and hearing loss, through a mechanism that has remained elusive. Using in silico, in vitro, and in vivo studies, we discovered defective mitophagy in XPA due to PARP1 hyperactivation and NAD + (and thus, SIRT1) depletion. This leads to mitochondrial membrane hyper-polarization, PINK1 cleavage and defective mitophagy. This study underscores the importance of mitophagy in promoting a healthy pool of mitochondria and in preventing neurodegeneration and premature aging.

Original languageEnglish
JournalAutophagy
Volume10
Issue number8
Pages (from-to)1468-1469
Number of pages2
ISSN1554-8627
DOIs
Publication statusPublished - 2014
Externally publishedYes

    Research areas

  • Autophagy, DNA repair, Mitophagy, SIRT1, Xeroderma pigmentosum group A

ID: 172128406