Contribution of defective mitophagy to the neurodegeneration in DNA repair-deficient disorders
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Contribution of defective mitophagy to the neurodegeneration in DNA repair-deficient disorders. / Scheibye-Knudsen, Morten; Fang, Evandro Fei; Croteau, Deborah L.; Bohr, Vilhelm A.
In: Autophagy, Vol. 10, No. 8, 2014, p. 1468-1469.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Contribution of defective mitophagy to the neurodegeneration in DNA repair-deficient disorders
AU - Scheibye-Knudsen, Morten
AU - Fang, Evandro Fei
AU - Croteau, Deborah L.
AU - Bohr, Vilhelm A.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - Autophagy
KW - DNA repair
KW - Mitophagy
KW - SIRT1
KW - Xeroderma pigmentosum group A
UR - http://www.scopus.com/inward/record.url?scp=84905908997&partnerID=8YFLogxK
U2 - 10.4161/auto.29321
DO - 10.4161/auto.29321
M3 - Journal article
C2 - 24991831
AN - SCOPUS:84905908997
VL - 10
SP - 1468
EP - 1469
JO - Autophagy
JF - Autophagy
SN - 1554-8627
IS - 8
ER -
ID: 172128406