scholarly journals The ER protein Creld regulates ER-mitochondria contact dynamics and respiratory complex 1 activity

2021 ◽  
Author(s):  
Marie Paradis ◽  
Nicole Kucharowski ◽  
Gabriela Edwards ◽  
Santiago Maya Palacios ◽  
Christian Meyer ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mitochondrial Dynamics ◽  
Contact Dynamics ◽  
New Paradigm ◽  
Respiratory Complex ◽  
Atrioventricular Septal Defects ◽  
Septal Defects ◽  
Respiratory Complex I ◽  
Complex I Activity

Abstract Dynamic contacts are formed between endoplasmic reticulum (ER) and mitochondria that enable the exchange of calcium and phospholipids. Disturbed contacts between ER and mitochondria impair mitochondrial dynamics and are a molecular hallmark of Parkinson’s disease. Cystein-rich with EGF-like domain (Creld) are ER-proteins associated with atrioventricular septal defects, but human CRELD1 is also a poorly characterized risk gene for Parkinson’s disease. Here we show that Creld is required for ER-mitochondria communication. Loss of Creld leads to mitochondrial hyperfusion and reduced ROS signaling in Drosophila melanogaster, Xenopus tropicalis and human cells. We found that reduced respiratory complex I activity lowers hydrogen peroxide levels, which disturbs neuronal activity and leads to impaired locomotion in Creld mutants. Our study presents a new paradigm of neuron dysfunction as a result of impaired ER-mitochondria communication and a new model for Parkinson’s disease.

scholarly journals Reduced Basal Autophagy and Impaired Mitochondrial Dynamics Due to Loss of Parkinson's Disease-Associated Protein DJ-1

PLoS ONE ◽  
2010 ◽  
Vol 5 (2) ◽  
pp. e9367 ◽  
Author(s):  
Guido Krebiehl ◽  
Sabine Ruckerbauer ◽  
Lena F. Burbulla ◽  
Nicole Kieper ◽  
Brigitte Maurer ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mitochondrial Dynamics

scholarly journals Parkinson's Disease Management: Towards a New Paradigm

1999 ◽  
Vol 26 (S2) ◽  
pp. S53-S57 ◽  
Author(s):  
Mark Guttman ◽  
Oksana Suchowersky
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Surgical Treatment ◽  
Disease Management ◽  
Management Strategy ◽  
Clinical Symptoms ◽  
Treatment Modalities ◽  
New Paradigm ◽  
The Past

Over the past decade, management of Parkinson's disease has changed significantly due to the expansion of medical and surgical treatment modalities. Neurologists now have the ability (and the challenge) of choosing from multiple medications to devise an individual management strategy for each patient depending on his/her clinical symptoms and needs. Several different surgical therapies are also available. The topics covered in this supplement have highlighted the new options that are now available, as well as the treatments that have been in clinical usage. This review attempts to synthesize the information that is currently available in an attempt to help clinical neurologists make the appropriate choice for their patients.

scholarly journals Mitochondrial Dynamics and Mitophagy in the 6-Hydroxydopamine Preclinical Model of Parkinson's Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Maria F. Galindo ◽  
Maria E. Solesio ◽  
Sandra Atienzar-Aroca ◽  
Maria J. Zamora ◽  
Joaquín Jordán Bueso
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Therapeutic Potential ◽  
Mitochondrial Dynamics ◽  
Second Messengers ◽  
Treatment Strategies ◽  
Preclinical Model ◽  
Molecular Signaling ◽  
Mitochondrial Division

We discuss the participation of mitochondrial dynamics and autophagy in the 6-hydroxidopamine-induced Parkinson’s disease model. The regulation of dynamic mitochondrial processes such as fusion, fission, and mitophagy has been shown to be an important mechanism controlling cellular fate. An imbalance in mitochondrial dynamics may contribute to both familial and sporadic neurodegenerative diseases including Parkinson’s disease. With special attention we address the role of second messengers as the role of reactive oxygen species and the mitochondria as the headquarters of cell death. The role of molecular signaling pathways, for instance, the participation of Dynamin-related protein 1(Drp1), will also be addressed. Furthermore evidence demonstrates the therapeutic potential of small-molecule inhibitors of mitochondrial division in Parkinson’s disease. For instance, pharmacological inhibition of Drp1, through treatment with the mitochondrial division inhibitor-1, results in the abrogation of mitochondrial fission and in a decrease of the number of autophagic cells. Deciphering the signaling cascades that underlie mitophagy triggered by 6-OHDA, as well as the mechanisms that determine the selectivity of this response, will help to better understand this process and may have impact on human treatment strategies of Parkinson’s disease.

scholarly journals Glucose Modulates Respiratory Complex I Activity in Response to Acute Mitochondrial Dysfunction

2012 ◽  
Vol 287 (46) ◽  
pp. 38729-38740 ◽  
Author(s):  
Giuseppe Cannino ◽  
Riyad El-Khoury ◽  
Marja Pirinen ◽  
Bettina Hutz ◽  
Pierre Rustin ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Complex I ◽  
Respiratory Complex ◽  
Respiratory Complex I ◽  
Complex I Activity

scholarly journals Mitochondrial Fusion/Fission, Transport and Autophagy in Parkinson's Disease: When Mitochondria Get Nasty

2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Daniela M. Arduíno ◽  
A. Raquel Esteves ◽  
Sandra M. Cardoso
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mitochondrial Dysfunction ◽  
Molecular Basis ◽  
Molecular Mechanisms ◽  
Mitochondrial Dynamics ◽  
Growing Body ◽  
Parkinsonian Disorders ◽  
Mitochondrial Trafficking

Understanding the molecular basis of Parkinson's disease (PD) has proven to be a major challenge in the field of neurodegenerative diseases. Although several hypotheses have been proposed to explain the molecular mechanisms underlying the pathogenesis of PD, a growing body of evidence has highlighted the role of mitochondrial dysfunction and the disruption of the mechanisms of mitochondrial dynamics in PD and other parkinsonian disorders. In this paper, we comment on the recent advances in how changes in the mitochondrial function and mitochondrial dynamics (fusion/fission, transport, and clearance) contribute to neurodegeneration, specifically focusing on PD. We also evaluate the current controversies in those issues and discuss the role of fusion/fission dynamics in the mitochondrial lifecycle and maintenance. We propose that cellular demise and neurodegeneration in PD are due to the interplay between mitochondrial dysfunction, mitochondrial trafficking disruption, and impaired autophagic clearance.

scholarly journals Parkinson's disease mutations in PINK1 result in decreased Complex I activity and deficient synaptic function

2009 ◽  
Vol 1 (2) ◽  
pp. 99-111 ◽  
Author(s):  
Vanessa A. Morais ◽  
Patrik Verstreken ◽  
Anne Roethig ◽  
Joél Smet ◽  
An Snellinx ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Complex I ◽  
Synaptic Function ◽  
Disease Mutations ◽  
Complex I Activity

scholarly journals Mitochondrial Dynamics and Parkinson's Disease: Focus on Parkin

2012 ◽  
Vol 16 (9) ◽  
pp. 935-949 ◽  
Author(s):  
Kah-Leong Lim ◽  
Xiao-Hui Ng ◽  
Lim Gui-Yin Grace ◽  
Tso-Pang Yao
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mitochondrial Dynamics ◽  
Disease Focus
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