Control of mitochondrial integrity in Parkinson's disease.
Parkinson's disease (PD) is the most common neurodegenerative movement disorder associated with a loss of dopaminergic neurons. The role of mitochondria in the aetiology of PD has been questioned for decades, mostly from the perspective of bioenergetic failure. For decades, a deficit in mitochondrial respiration was thought to be a key factor in PD neurodegeneration. However, excluding a few exceptions where a clinical picture of parkinsonism is associated with a mitochondrial DNA mutation, preclinical and clinical studies have failed to identify any genetic mutations in the genes encoding for the electron transport chain complexes in PD patients. More recently, it has been discovered that mutations in the genes encoding for Parkin, PINK1 (PTEN-induced putative kinase-1) and DJ-1 are associated with familial forms of PD and with mitochondrial alterations, including morphological abnormalities. These results have led many researchers to revisit the question of mitochondrial biology as a primary mechanism in PD pathogenesis, this time from an angle of perturbation in mitochondrial dynamics and not from the angle of a deficit in respiration.
Vives-Bauza
Cristofol
C
Department of Neurology, Motor Neuron Biology and Disease, Columbia University, New York, NY, USA.
Tocilescu
Maja
M
Devries
Rosa L A
RL
Alessi
Dana M
DM
Jackson-Lewis
Vernice
V
Przedborski
Serge
S
D001343:Autophagy / Q000502:physiology*; D019069:Cell Respiration / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D015513:Oncogene Proteins / Q000235:genetics; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology*; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D000099202:PTEN-Induced Putative Kinase
D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases; D044767:Ubiquitin-Protein Ligases; D000099202:PTEN-Induced Putative Kinase; C111567:parkin protein; C105131:PARK7 protein, human