Autophagy and the degradation of mitochondria

Goldman, Scott J.; Taylor, Robert H.; Zhang, Yong; Jin, Shengkan

doi:10.1016/j.mito.2010.01.005

Cited by 132 publications

(93 citation statements)

References 77 publications

(82 reference statements)

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“…Recruitment of Parkin was followed by removal of these damaged mitochondria through a specialized form of autophagy known as mitophagy, in which mitochondria are specifically degraded following engulfment by autophagosomes (for review, see Goldman et al 2010). Recent findings suggest that mitophagy is intimately linked with changes in mitochondrial size and shape brought about through fission and fusion (for review, see Hyde et al 2010).…”

Section: Pink1 and Parkin Promote Mitophagymentioning

confidence: 99%

Drosophila as a Model to Study Mitochondrial Dysfunction in Parkinson's Disease

Guo¹

2012

Cold Spring Harbor Perspectives in Medicine

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Identification of single gene mutations that lead to inherited forms of Parkinson's disease (PD) has provided strong impetus for the use of animal models to study normal functions of these "PD genes" and the cellular defects that occur in the presence of pathogenic PD mutations. Drosophila has emerged as an effective model in PD-related gene studies. Important insights into the cellular basis of PD pathogenesis include the demonstration that two PD genes, PINK1 and parkin, function in a common pathway, with PINK1 positively regulating parkin, to control mitochondrial integrity and maintenance. This is accomplished through regulation of mitochondrial fission/fusion dynamics. Subsequent observations in both fly and mammalian systems showed that these proteins are important for sensing mitochondrial damage and recruiting damaged mitochondria to the quality-control machinery for subsequent removal. Here, I begin by reviewing the opportunities and challenges to understanding PD pathogenesis and developing new therapies. I then review the unique tools and technologies available in Drosophila for studying PD genes. Subsequently, I review lessons that we have learned from studies in Drosophila, emphasizing the PINK1/parkin pathway, as well as studies of DJ-1 and Omi/HtrA2, two additional genes associated with PD implicated in regulation of mitochondrial function. I end by discussing how Drosophila can be used to further probe the functions of PINK1 and parkin, and the regulation of mitochondrial quality more generally. In additional to PD, defects in mitochondrial function are associated with normal aging and with many diseases of aging. Thus, insights gained from the studies of mitochondrial dynamics and quality control in Drosophila are likely to be of general significance. Parkinson's disease (PD) is the second most common neurodegenerative disorder, with a prevalence second only to that of Alzheimer's disease. There is no cure or treatment that can halt disease progression. A primary pathological hallmark of the disease is degeneration of multiple neuronal types including, most notably, dopaminergic neurons in the substantia nigra of the midbrain (Dauer and Przedborski 2003;Shulman et al. 2011). However, pathology of many non-dopaminergic neurons including olfactory and brain stem neurons predates that of DA neurons (Braak et al. 2003). Patients with PD present with characteristic "motor symptoms," such as resting tremor, slowness of movement, rigidity, postural instability, and gait difficulty. Although the mainstay of current medical treatment for PD is dopamine replacement, this is not very satisfying. First, the dopamine replacement only alleviates some of the motor symptoms (does not help gait problems), becomes less effective over time, and is often associated with intolerable side effects. Second, PD patients also present with a combination of non-motor symptoms (Simuni and Sethi 2008) including dementia, which occurs in more than one-third of patients; psychiatric symptoms such as depression, anxiety, and ob...

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Section: Pink1 and Parkin Promote Mitophagymentioning

confidence: 99%

Drosophila as a Model to Study Mitochondrial Dysfunction in Parkinson's Disease

Guo¹

2012

Cold Spring Harbor Perspectives in Medicine

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“…Therefore, it was suggested that the two proteins could act in common pathways, with parkin working downstream of PINK1, since transgenic expression of parkin rescued all PINK1 impairments, but not the contrary [243,250,251]. Goldman et al(2010) [252], described that PINK1 and parkin both display a role in the mitochondrial targeting of autophagy, a process by which the cells degrade intracellular material through lysosomes. Mitophagy, which is the mitochondrialͲ specific form of this process, is important in the control of damaged or stressed cellular organelles.…”

Section: Ptenǧinduced Putative Kinase 1 (Pink1)mentioning

confidence: 99%

Revisiting oxidative stress and mitochondrial dysfunction in the pathogenesis of Parkinson disease—resemblance to the effect of amphetamine drugs of abuse

Perfeito

Cunha‐Oliveira

Rego

2012

Free Radical Biology and Medicine

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“…Maintenance mitophagy serves to keep a healthy pool of mitochondria by clearing aging mitochondria. 10 While the specific signals that initiate autophagic clearance of mitochondria are still being fully described, loss of mitochondrial membrane potential appears to be strongly associated with removal by mitophagy.…”

Section: Introductionmentioning

confidence: 99%