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Mitochondrial dynamics, cell death and the pathogenesis of Parkinson's disease.
Apoptosis. 2010 Nov; 15(11):1336-53.A

Abstract

The structure and function of the mitochondrial network is regulated by mitochondrial biogenesis, fission, fusion, transport and degradation. A well-maintained balance of these processes (mitochondrial dynamics) is essential for neuronal signaling, plasticity and transmitter release. Core proteins of the mitochondrial dynamics machinery play important roles in the regulation of apoptosis, and mutations or abnormal expression of these factors are associated with inherited and age-dependent neurodegenerative disorders. In Parkinson's disease (PD), oxidative stress and mitochondrial dysfunction underlie the development of neuropathology. The recessive Parkinsonism-linked genes PTEN-induced kinase 1 (PINK1) and Parkin maintain mitochondrial integrity by regulating diverse aspects of mitochondrial function, including membrane potential, calcium homeostasis, cristae structure, respiratory activity, and mtDNA integrity. In addition, Parkin is crucial for autophagy-dependent clearance of dysfunctional mitochondria. In the absence of PINK1 or Parkin, cells often develop fragmented mitochondria. Whereas excessive fission may cause apoptosis, coordinated induction of fission and autophagy is believed to facilitate the removal of damaged mitochondria through mitophagy, and has been observed in some types of cells. Compensatory mechanisms may also occur in mice lacking PINK1 that, in contrast to cells and Drosophila, have only mild mitochondrial dysfunction and lack dopaminergic neuron loss. A better understanding of the relationship between the specific changes in mitochondrial dynamics/turnover and cell death will be instrumental to identify potentially neuroprotective pathways steering PINK1-deficient cells towards survival. Such pathways may be manipulated in the future by specific drugs to treat PD and perhaps other neurodegenerative disorders characterized by abnormal mitochondrial function and dynamics.

Authors+Show Affiliations

Department of Anatomy and Neurobiology, University of Kentucky, 800 Rose Street, Lexington, KY 40536, USA. hansruedi.bueler@uky.edu

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

20131004

Citation

Büeler, Hansruedi. "Mitochondrial Dynamics, Cell Death and the Pathogenesis of Parkinson's Disease." Apoptosis : an International Journal On Programmed Cell Death, vol. 15, no. 11, 2010, pp. 1336-53.
Büeler H. Mitochondrial dynamics, cell death and the pathogenesis of Parkinson's disease. Apoptosis. 2010;15(11):1336-53.
Büeler, H. (2010). Mitochondrial dynamics, cell death and the pathogenesis of Parkinson's disease. Apoptosis : an International Journal On Programmed Cell Death, 15(11), 1336-53. https://doi.org/10.1007/s10495-010-0465-0
Büeler H. Mitochondrial Dynamics, Cell Death and the Pathogenesis of Parkinson's Disease. Apoptosis. 2010;15(11):1336-53. PubMed PMID: 20131004.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mitochondrial dynamics, cell death and the pathogenesis of Parkinson's disease. A1 - Büeler,Hansruedi, PY - 2010/2/5/entrez PY - 2010/2/5/pubmed PY - 2011/3/24/medline SP - 1336 EP - 53 JF - Apoptosis : an international journal on programmed cell death JO - Apoptosis VL - 15 IS - 11 N2 - The structure and function of the mitochondrial network is regulated by mitochondrial biogenesis, fission, fusion, transport and degradation. A well-maintained balance of these processes (mitochondrial dynamics) is essential for neuronal signaling, plasticity and transmitter release. Core proteins of the mitochondrial dynamics machinery play important roles in the regulation of apoptosis, and mutations or abnormal expression of these factors are associated with inherited and age-dependent neurodegenerative disorders. In Parkinson's disease (PD), oxidative stress and mitochondrial dysfunction underlie the development of neuropathology. The recessive Parkinsonism-linked genes PTEN-induced kinase 1 (PINK1) and Parkin maintain mitochondrial integrity by regulating diverse aspects of mitochondrial function, including membrane potential, calcium homeostasis, cristae structure, respiratory activity, and mtDNA integrity. In addition, Parkin is crucial for autophagy-dependent clearance of dysfunctional mitochondria. In the absence of PINK1 or Parkin, cells often develop fragmented mitochondria. Whereas excessive fission may cause apoptosis, coordinated induction of fission and autophagy is believed to facilitate the removal of damaged mitochondria through mitophagy, and has been observed in some types of cells. Compensatory mechanisms may also occur in mice lacking PINK1 that, in contrast to cells and Drosophila, have only mild mitochondrial dysfunction and lack dopaminergic neuron loss. A better understanding of the relationship between the specific changes in mitochondrial dynamics/turnover and cell death will be instrumental to identify potentially neuroprotective pathways steering PINK1-deficient cells towards survival. Such pathways may be manipulated in the future by specific drugs to treat PD and perhaps other neurodegenerative disorders characterized by abnormal mitochondrial function and dynamics. SN - 1573-675X UR - https://www.unboundmedicine.com/medline/citation/20131004/Mitochondrial_dynamics_cell_death_and_the_pathogenesis_of_Parkinson's_disease_ L2 - https://doi.org/10.1007/s10495-010-0465-0 DB - PRIME DP - Unbound Medicine ER -