PINK1 function in health and disease

被引:109
作者
Deas, Emma [1 ]
Plun-Favreau, Helene [1 ]
Wood, Nicholas W. [1 ]
机构
[1] UCL Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England
基金
英国医学研究理事会;
关键词
calcium signalling; mitochondria; oxidative stress; PINK1; PARKINSONS-DISEASE; OXIDATIVE STRESS; MITOCHONDRIAL DYSFUNCTION; PROTECTS NEURONS; QUALITY-CONTROL; COENZYME Q(10); FUSION; PROTEASE; DYNAMICS; NEURODEGENERATION;
D O I
10.1002/emmm.200900024
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
The role of mitochondria in sporadic Parkinson's disease (PD) has been debated for a little over 20 years since the description of complex I deficiency in the substantia nigra pars compacta (SNpc) of PD patients. However, the identification of recessive pathogenic mutations in the pink1 gene in familial PD cases firmly re-ignited interest in the pathophysiology of mitochondria in PD. PINK1 is a putative mitochondrial serine/threonine kinase, which protects cells against oxidative stress induced apoptosis. The mechanism by which this is achieved and the effect of the pathogenic mutations has been an area of intensive research over the past five years. Significant progress has been made and, in this review, we summarize the physiological roles that have been assigned to PINK1 and the potential mechanisms behind pathogenesis.
引用
收藏
页码:152 / 165
页数:14
相关论文
共 85 条
[1]   A heterozygous effect for PINK1 mutations in Parkinson's disease? [J].
Abou-Sleiman, Patrick M. ;
Muqit, Miratul M. K. ;
McDonald, Neil Q. ;
Yang, Yan Xiang ;
Gandhi, Sonia ;
Healy, Daniel G. ;
Harvey, Kirsten ;
Harvey, Robert J. ;
Deas, Emma ;
Hatia, Kailash ;
Quinn, Niall ;
Lees, Andrew ;
Latchman, David S. ;
Wood, Nicholas W. .
ANNALS OF NEUROLOGY, 2006, 60 (04) :414-419
[2]   Loss of PINK1 function affects development and results in neurodegeneration in zebrafish [J].
Anichtchik, Oleg ;
Diekmann, Heike ;
Fleming, Angeleen ;
Roach, Alan ;
Goldsmith, Paul ;
Rubinsztein, David C. .
JOURNAL OF NEUROSCIENCE, 2008, 28 (33) :8199-8207
[3]   Mitochondria, oxidants, and aging [J].
Balaban, RS ;
Nemoto, S ;
Finkel, T .
CELL, 2005, 120 (04) :483-495
[4]   Depletion of 26S proteasomes in mouse brain neurons causes neurodegeneration and Lewy-like inclusions resembling human pale bodies [J].
Bedford, Lynn ;
Hay, David ;
Devoy, Anny ;
Paine, Simon ;
Powe, Des G. ;
Seth, Rashmi ;
Gray, Trevor ;
Topham, Ian ;
Fone, Kevin ;
Rezvani, Nooshin ;
Mee, Maureen ;
Soane, Tim ;
Layfield, Robert ;
Sheppard, Paul W. ;
Ebendal, Ted ;
Usoskin, Dmitry ;
Lowe, James ;
Mayer, R. John .
JOURNAL OF NEUROSCIENCE, 2008, 28 (33) :8189-8198
[5]   Dopaminergic midbrain neurons are the prime target for mitochondrial DNA deletions [J].
Bender, Andreas ;
Schwarzkopf, Rachel-Maria ;
McMillan, Anja ;
Krishnan, Kim J. ;
Rieder, Gabriele ;
Neumann, Manuela ;
Elstner, Matthias ;
Turnbull, Douglas M. ;
Klopstock, Thomas .
JOURNAL OF NEUROLOGY, 2008, 255 (08) :1231-1235
[6]   Mitochondrial fission and fusion dynamics: the long and short of it [J].
Berman, S. B. ;
Pineda, F. J. ;
Hardwick, J. M. .
CELL DEATH AND DIFFERENTIATION, 2008, 15 (07) :1147-1152
[7]   Regulation of mitochondrial structure and function by the F1FO-ATPase inhibitor protein, IF1 [J].
Campanella, Michelangelo ;
Casswell, Edward ;
Chong, Stephanie ;
Farah, Ziad ;
Wieckowski, Mariusz R. ;
Abramov, Andrey Y. ;
Tinker, Andrew ;
Duchen, Michael R. .
CELL METABOLISM, 2008, 8 (01) :13-25
[8]   'Rejuvenation' protects neurons in mouse models of Parkinson's disease [J].
Chan, C. Savio ;
Guzman, Jaime N. ;
Ilijic, Ema ;
Mercer, Jeff N. ;
Rick, Caroline ;
Tkatch, Tatiana ;
Meredith, Gloria E. ;
Surmeier, D. James .
NATURE, 2007, 447 (7148) :1081-U5
[9]   Mitochondrial fusion and fission in mammals [J].
Chan, David C. .
ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, 2006, 22 :79-99
[10]   Disruption of fusion results in mitochondrial heterogeneity and dysfunction [J].
Chen, HC ;
Chomyn, A ;
Chan, DC .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (28) :26185-26192