The PINK1/Parkin-mediated mitophagy is compromised by PD-associated mutations

Geisler, Sven; Holmström, Kira M.; Treis, Angela; Skujat, Diana; Weber, Stephanie; Fiesel, Fabienne C.; Kahle, Philipp J.; Springer, Wolfdieter

doi:10.4161/auto.6.7.13286

Cited by 276 publications

(222 citation statements)

References 26 publications

Supporting

Mentioning

211

Contrasting

Unclassified

Order By: Relevance

“…[9][10][11][12][13] Ubiquitination by PARK2 and proteasomal degradation of the OMM mitochondrial fission proteins MFN1/2 are early events triggered by ΔΨ collapse; 14 this study provided the first indication that the proteasome is also required for effective mitochondrial clearance. This machinery is critical for the PARK2-dependent proteolysis of a series of OMM proteins, a process associated with OMM rupture that precedes the degradation of dysfunctional organelles by autophagy.…”

Section: Introductionmentioning

confidence: 75%

The TOMM machinery is a molecular switch in PINK1 and PARK2/PARKIN-dependent mitochondrial clearance

et al. 2013

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 75%

The TOMM machinery is a molecular switch in PINK1 and PARK2/PARKIN-dependent mitochondrial clearance

et al. 2013

View full text Add to dashboard Cite

“…This is evident especially in PD, where impaired mitochondrial dynamics and oxidative stress are among the main characteristics of the disease (Narendra et al 2008;Buttner et al 2008;Geisler et al 2010b). p62/SQSTM1 aids in clearing dysfunctional mitochondria tagged for degradation by the Pink1-Parkin system, two genes involved in familial PD (see above and (Narendra et al 2010a;Geisler et al 2010a)).…”

Section: Neurodegenerative Diseasesmentioning

confidence: 99%

p62/SQSTM1 at the interface of aging, autophagy, and disease

Bitto

Lerner

Nacarelli

et al. 2014

AGE

124

View full text Add to dashboard Cite

Advanced age is characterized by increased incidence of many chronic, noninfectious diseases that impair the quality of living of the elderly and pose a major burden on the healthcare systems of developed countries. These diseases are characterized by impaired or altered function at the tissue and cellular level, which is a hallmark of the aging process. Age-related impairments are likely due to loss of homeostasis at the cellular level, which leads to the accumulation of dysfunctional organelles and damaged macromolecules, such as proteins, lipids, and nucleic acids. Intriguingly, aging and age-related diseases can be delayed by modulating nutrient signaling pathways converging on the target of rapamycin (TOR) kinase, either by genetic or dietary intervention. TOR signaling influences aging through several potential mechanisms, such as autophagy, a degradation pathway that clears the dysfunctional organelles and damaged macromolecules that accumulate with aging. Autophagy substrates are targeted for degradation by associating with p62/SQSTM1, a multidomain protein that interacts with the autophagy machinery. p62/SQSTM1 is involved in several cellular processes, and its loss has been linked to accelerated aging and to age-related pathologies. In this review, we describe p62/SQSTM1, its role in autophagy and in signaling pathways, and its emerging role in aging and age-associated pathologies. Finally, we propose p62/ SQSTM1 as a novel target for aging studies and ageextending interventions.

show abstract

“…The mitochondrial recruitment of Parkin induces the ubiquitination of several mitochondrial proteins such as VDAC, Mfn1 and Mfn2 (Gegg et al, 2010;Geisler et al, 2010). This phenomenon is followed by the recruitment of ubiquitin-binding autophagic components that leads to mitochondrial clearance, and could also aid the mitochondrial fission necessary for mitophagy to occur.…”

Section: Linking Oxidative Stress and Mitochondrial Dynamics In Pd Amentioning

confidence: 99%

Mitochondrial respiratory chain dysfunction: Implications in neurodegeneration

Morán

Moreno-Lastres

Marín-Buera

et al. 2012

Free Radical Biology and Medicine

144

View full text Add to dashboard Cite

For decades mitochondria have been considered static round shaped organelles in charge of energy production. On the contrary, they are highly dynamic cellular components that undergo continuous cycles of fusion and fission influenced, for instance, by oxidative stress, cellular energy requirements, or the cell cycle state. New important functions beyond energy production have been attributed to mitochondria, such as the regulation of cell survival due to their role in the modulation of apoptosis, autophagy and aging. Primary mitochondrial diseases due to mutations in genes involved in these new mitochondrial functions, and the implication of mitochondrial dysfunction in multifactorial human pathologies like cancer, Alzheimer's and Parkinson's diseases, or diabetes has been demonstrated. Therefore, mitochondria are set at a central point of the equilibrium between health and disease, and a better understanding of mitochondrial functions will open new fields to explore the role of these mitochondrial pathways in human pathologies. The present review will dissect the relationships between the activity and assembly defects of the mitochondrial respiratory chain, oxidative damage, and alterations in mitochondrial dynamics, with special focus at their implications in neurodegeneration.

show abstract

The PINK1/Parkin-mediated mitophagy is compromised by PD-associated mutations

Cited by 276 publications

References 26 publications

The TOMM machinery is a molecular switch in PINK1 and PARK2/PARKIN-dependent mitochondrial clearance

The TOMM machinery is a molecular switch in PINK1 and PARK2/PARKIN-dependent mitochondrial clearance

p62/SQSTM1 at the interface of aging, autophagy, and disease

Mitochondrial respiratory chain dysfunction: Implications in neurodegeneration

Contact Info

Product

Resources

About