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Parkin loss leads to PARIS-dependent declines in mitochondrial mass and respiration.
Stevens, Daniel A; Lee, Yunjong; Kang, Ho Chul; Lee, Byoung Dae; Lee, Yun-Il; Bower, Aaron; Jiang, Haisong; Kang, Sung-Ung; Andrabi, Shaida A; Dawson, Valina L; Shin, Joo-Ho; Dawson, Ted M.
Afiliação
  • Stevens DA; Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; Solomon H. Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; Adrienne Helis Malvin Medical Research F
  • Lee Y; Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; Adrienne Helis Malvin Medical Research Foundation, New Orleans, LA 70130-2685; Diana Helis Henry Medical Research Foundation, New Orleans, LA 70130-2685; De
  • Kang HC; Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; Department of Physiology, Ajou University School of Medicine,
  • Lee BD; Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; Age-Related and Brain Disease Research Center, Department of
  • Lee YI; Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; Well Aging Research Center, Samsung Advanced Institute of Tec
  • Bower A; Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; Adrienne Helis Malvin Medical Research Foundation, New Orleans, LA 70130-2685;
  • Jiang H; Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; Adrienne Helis Malvin Medical Research Foundation, New Orleans, LA 70130-2685; Diana Helis Henry Medical Research Foundation, New Orleans, LA 70130-2685; De
  • Kang SU; Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; Adrienne Helis Malvin Medical Research Foundation, New Orleans, LA 70130-2685; Diana Helis Henry Medical Research Foundation, New Orleans, LA 70130-2685; De
  • Andrabi SA; Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205;
  • Dawson VL; Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; Solomon H. Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; Adrienne Helis Malvin Medical Research F
  • Shin JH; Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; Division of Pharmacology, Department of Molecular Cell Biolog
  • Dawson TM; Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; Solomon H. Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; Adrienne Helis Malvin Medical Research F
Proc Natl Acad Sci U S A ; 112(37): 11696-701, 2015 Sep 15.
Article em En | MEDLINE | ID: mdl-26324925
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Ubiquitina-Proteína Ligases / Mitocôndrias Limite: Animals / Humans / Male Idioma: En Ano de publicação: 2015 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Ubiquitina-Proteína Ligases / Mitocôndrias Limite: Animals / Humans / Male Idioma: En Ano de publicação: 2015 Tipo de documento: Article