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Parkin loss leads to PARIS-dependent declines in mitochondrial mass and respiration.

Authors
Stevens, DA | Lee, Y | Kang, HC  | Lee, BD | Lee, YI | Bower, A | Jiang, H | Kang, SU | Andrabi, SA | Dawson, VL | Shin, JH | Dawson, TM
Citation
Proceedings of the National Academy of Sciences of the United States of America, 112(37). : 11696-11701, 2015
Journal Title
Proceedings of the National Academy of Sciences of the United States of America
ISSN
0027-84241091-6490
Abstract
Mutations in parkin lead to early-onset autosomal recessive Parkinson's disease (PD) and inactivation of parkin is thought to contribute to sporadic PD. Adult knockout of parkin in the ventral midbrain of mice leads to an age-dependent loss of dopamine neurons that is dependent on the accumulation of parkin interacting substrate (PARIS), zinc finger protein 746 (ZNF746), and its transcriptional repression of PGC-1α. Here we show that adult knockout of parkin in mouse ventral midbrain leads to decreases in mitochondrial size, number, and protein markers consistent with a defect in mitochondrial biogenesis. This decrease in mitochondrial mass is prevented by short hairpin RNA knockdown of PARIS. PARIS overexpression in mouse ventral midbrain leads to decreases in mitochondrial number and protein markers and PGC-1α-dependent deficits in mitochondrial respiration. Taken together, these results suggest that parkin loss impairs mitochondrial biogenesis, leading to declining function of the mitochondrial pool and cell death.
MeSH

DOI
10.1073/pnas.1500624112
PMID
26324925
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Physiology
Ajou Authors
강, 호철
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