scholarly journals Deficiency of Parkinson’s disease-related gene Fbxo7 is associated with impaired mitochondrial metabolism by PARP activation

2016 ◽  
Vol 24 (1) ◽  
pp. 120-131 ◽  
Author(s):  
Marta Delgado-Camprubi ◽  
Noemi Esteras ◽  
Marc PM Soutar ◽  
Helene Plun-Favreau ◽  
Andrey Y Abramov
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Complex I ◽  
Parp Inhibitor ◽  
Parp Activation ◽  
Mitochondrial Homeostasis ◽  
Transport Chain ◽  
Ubiquitin Ligase Complex ◽  
F Box Protein ◽  
Redox Index

Abstract The Parkinson’s disease (PD)-related protein F-box only protein 7 (Fbxo7) is the substrate-recognition component of the Skp1-Cullin-F-box protein E3 ubiquitin ligase complex. We have recently shown that PD-associated mutations in Fbxo7 disrupt mitochondrial autophagy (mitophagy), suggesting a role for Fbxo7 in modulating mitochondrial homeostasis. Here we report that Fbxo7 deficiency is associated with reduced cellular NAD+ levels, which results in increased mitochondrial NADH redox index and impaired activity of complex I in the electron transport chain. Under these conditions of compromised respiration, mitochondrial membrane potential and ATP contents are reduced, and cytosolic reactive oxygen species (ROS) production is increased. ROS activates poly (ADP-ribose) polymerase (PARP) activity in Fbxo7-deficient cells. PARP inhibitor restores cellular NAD+ content and redox index and ATP pool, suggesting that PARP overactivation is cause of decreased complex I-driven respiration. These findings bring new insight into the mechanism of Fbxo7 deficiency, emphasising the importance of mitochondrial dysfunction in PD.

Monitoring mitochondrial dynamics and complex I dysfunction in neurons: implications for Parkinson's disease

2013 ◽  
Vol 41 (6) ◽  
pp. 1618-1624 ◽  
Author(s):  
Eve M. Simcox ◽  
Amy Reeve ◽  
Doug Turnbull
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Complex I ◽  
Neurodegenerative Disorder ◽  
Mitochondrial Dynamics ◽  
Cell Loss ◽  
Transport Chain ◽  
The Individual ◽  
And Function ◽  
Energy Dependent

Mitochondrial dynamics are essential for maintaining organelle stability and function. Through fission, fusion and mitophagic events, optimal populations of mitochondria are retained. Subsequently, alterations in such processes can have profound effects on the individual mitochondrion and the cell within which they reside. Neurons are post-mitotic energy-dependent cells and, as such, are particularly vulnerable to alterations in cellular bioenergetics and increased stress that may occur as a direct or indirect result of mitochondrial dysfunction. The trafficking of mitochondria to areas of higher energy requirements, such as synapses, where mitochondrial densities fluctuate, further highlights the importance of efficient mitochondrial dynamics in neurons. PD (Parkinson's disease) is a common progressive neurodegenerative disorder which is characterized by the loss of dopaminergic neurons within the substantia nigra. Complex I, the largest of all of the components of the electron transport chain is heavily implicated in PD pathogenesis. The exact series of events that lead to cell loss, however, are not fully elucidated, but are likely to involve dysfunction of mitochondria, their trafficking and dynamics.

scholarly journals Mitochondrial Function and Parkinson’s Disease: From the Perspective of the Electron Transport Chain

2021 ◽  
Vol 14 ◽  
Author(s):  
Jeng-Lin Li ◽  
Tai-Yi Lin ◽  
Po-Lin Chen ◽  
Ting-Ni Guo ◽  
Shu-Yi Huang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Electron Transport ◽  
Complex I ◽  
Electron Transport Chain ◽  
Direct Evidence ◽  
Complex Iii ◽  
Complex Iv ◽  
Transport Chain ◽  
Mitochondrial Functions

Parkinson’s disease (PD) is known as a mitochondrial disease. Some even regarded it specifically as a disorder of the complex I of the electron transport chain (ETC). The ETC is fundamental for mitochondrial energy production which is essential for neuronal health. In the past two decades, more than 20 PD-associated genes have been identified. Some are directly involved in mitochondrial functions, such as PRKN, PINK1, and DJ-1. While other PD-associate genes, such as LRRK2, SNCA, and GBA1, regulate lysosomal functions, lipid metabolism, or protein aggregation, some have been shown to indirectly affect the electron transport chain. The recent identification of CHCHD2 and UQCRC1 that are critical for functions of complex IV and complex III, respectively, provide direct evidence that PD is more than just a complex I disorder. Like UQCRC1 in preventing cytochrome c from release, functions of ETC proteins beyond oxidative phosphorylation might also contribute to the pathogenesis of PD.

scholarly journals PINK1: A Bridge between Mitochondria and Parkinson’s Disease

Life ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 371
Author(s):  
Filipa Barroso Gonçalves ◽  
Vanessa Alexandra Morais
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Quality Control ◽  
High Energy ◽  
Common Denominator ◽  
Mitochondrial Quality Control ◽  
Mitochondrial Homeostasis ◽  
Cellular Environment ◽  
Familial Form ◽  
Mitochondrial Functions

Mitochondria are known as highly dynamic organelles essential for energy production. Intriguingly, in the recent years, mitochondria have revealed the ability to maintain cell homeostasis and ultimately regulate cell fate. This regulation is achieved by evoking mitochondrial quality control pathways that are capable of sensing the overall status of the cellular environment. In a first instance, actions to maintain a robust pool of mitochondria take place; however, if unsuccessful, measures that lead to overall cell death occur. One of the central key players of these mitochondrial quality control pathways is PINK1 (PTEN-induce putative kinase), a mitochondrial targeted kinase. PINK1 is known to interact with several substrates to regulate mitochondrial functions, and not only is responsible for triggering mitochondrial clearance via mitophagy, but also participates in maintenance of mitochondrial functions and homeostasis, under healthy conditions. Moreover, PINK1 has been associated with the familial form of Parkinson’s disease (PD). Growing evidence has strongly linked mitochondrial homeostasis to the central nervous system (CNS), a system that is replenished with high energy demanding long-lasting neuronal cells. Moreover, sporadic cases of PD have also revealed mitochondrial impairments. Thus, one could speculate that mitochondrial homeostasis is the common denominator in these two forms of the disease, and PINK1 may play a central role in maintaining mitochondrial homeostasis. In this review, we will discuss the role of PINK1 in the mitochondrial physiology and scrutinize its role in the cascade of PD pathology.

Beneficial effect of rice bran extract against rotenone-induced experimental Parkinson’s disease in rats

2021 ◽  
Vol 14 ◽  
Author(s):  
Sachin Kumar ◽  
Puneet Kumar
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rice Bran ◽  
Motor Coordination ◽  
Hexane Extract ◽  
Brain Disorder ◽  
Biochemical Alterations ◽  
Transport Chain ◽  
Behavioral Parameters ◽  
Per Oral

Background: Neurodegenerative diseases have become the rising cause of various disabilities worldwide, followed by aging, including Parkinson’s disease (PD). Parkinson’s disease is a degenerative brain disorder distinguished by growing motor & non-motor failure due to the degeneration of medium-sized spiked neurons in the striatum region. Rotenone is often employed to originate the animal model of PD. It is a powerful blocker of mitochondrial complex-I, mitochondrial electron transport chain that reliably produces Parkinsonism-like symptoms in rats. Rice bran (RB) is very rich in polyunsaturated fatty acids (PUFA) and nutritionally beneficial compounds such as γ-oryzanol, tocopherols, and tocotrienols and sterols are believed to have favorable outcomes on oxidative stress & mitochondrial function. Objective: The present study has been designed to explore RB extract’s effect against rotenone-induced neurotoxicity in rats. Method: In the present study, Rotenone (2 mg/kg, s.c) was administered systemically for 28 days. The hexane extract of RB was prepared using Soxhlation. Hexane extract (250 & 500 mg/kg) was administered per oral for 28 days in rotenone treated groups. Behavioral parameters (grip strength, motor coordination, locomotion, and catalepsy) were conducted on the 7th, 14th, 21st, and 28th day. Animals were sacrificed on the 29th day for biochemical estimation in the striatum and cortex. Result: This study demonstrates significant alteration in behavioral parameters, oxidative burden (increased lipid peroxidation, nitrite concentration, and decreased glutathione, catalase, SOD) in rotenone treated animals. Administration of hexane extract of RB prevented the behavioral, biochemical alterations induced by rotenone. The current research has been sketched to inspect RB extract’s effect against rotenone-developed neurotoxicity in rats. Conclusion: The findings support that PD is associated with impairments in motor activity. The results also suggest that the nutraceutical rice bran that contains γ-oryzanol, Vitamin-E, ferulic acid etc., may underlie the adjuvant susceptibility towards rotenone-induced PD in experimental rats.

scholarly journals Mitochondrial Complex I Reversible S-Nitrosation Improves Bioenergetics and Is Protective in Parkinson's Disease

2018 ◽  
Vol 28 (1) ◽  
pp. 44-61 ◽  
Author(s):  
Chiara Milanese ◽  
Victor Tapias ◽  
Sylvia Gabriels ◽  
Silvia Cerri ◽  
Giovanna Levandis ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Complex I ◽  
Mitochondrial Complex I ◽  
Mitochondrial Complex

scholarly journals Complex I and Parkinson's Disease

IUBMB Life ◽  
2001 ◽  
Vol 52 (3-5) ◽  
pp. 135-141 ◽  
Author(s):  
J. Timothy Greenamyre ◽  
Todd B. Sherer ◽  
Ranjita Betarbet ◽  
Alexander V. Panov
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Complex I
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