Environmental toxins and Parkinson’s disease: Putative roles of impaired electron transport chain and oxidative stress

2010 ◽  
Vol 26 (2) ◽  
pp. 121-128 ◽  
Author(s):  
Ibrahim Abdulwahid Arif ◽  
Haseeb Ahmad Khan

Despite recent advancements in the biomedical fields, the etiology and pathogenesis of Parkinson’s disease (PD) is still poorly understood, though the crucial roles of oxidative stress and impaired mitochondrial respiration have been suggested in the development of PD. The oxidative modification of the proteins of mitochondrial electron transport chain alters their normal function leading to the state of energy crisis in neurons. Exposure of environmental chemicals such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and rotenone in mouse produces the symptoms akin to PD and therefore these neurotoxins are commonly used in experimental studies on PD. Another environmental toxin, paraquat (a commonly used herbicide) has also been implicated with the onset of PD. The neurotoxicity of these chemicals is accompanied by the blockade of electron flow from NADH dehydrogenase to coenzyme Q. The agents with the ability to improve mitochondrial respiration and ATP production have been shown to exert beneficial effects in PD patients as well as in the animal models of PD. This review summarizes the current research implicating the impairment of mitochondrial respiratory chain and the role of environmental toxins in the pathogenesis of PD.

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Sandrine C. Foti ◽  
Iain Hargreaves ◽  
Stephanie Carrington ◽  
Aoife P. Kiely ◽  
Henry Houlden ◽  
...  

2021 ◽  
Vol 14 ◽  
Author(s):  
Jeng-Lin Li ◽  
Tai-Yi Lin ◽  
Po-Lin Chen ◽  
Ting-Ni Guo ◽  
Shu-Yi Huang ◽  
...  

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.


Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1874
Author(s):  
Suwei Chen ◽  
Sarah J. Annesley ◽  
Rasha A. F. Jasim ◽  
Paul R. Fisher

Mitochondrial dysfunction has been implicated in the pathology of Parkinson’s disease (PD). In Dictyostelium discoideum, strains with mitochondrial dysfunction present consistent, AMPK-dependent phenotypes. This provides an opportunity to investigate if the loss of function of specific PD-associated genes produces cellular pathology by causing mitochondrial dysfunction with AMPK-mediated consequences. DJ-1 is a PD-associated, cytosolic protein with a conserved oxidizable cysteine residue that is important for the protein’s ability to protect cells from the pathological consequences of oxidative stress. Dictyostelium DJ-1 (encoded by the gene deeJ) is located in the cytosol from where it indirectly inhibits mitochondrial respiration and also exerts a positive, nonmitochondrial role in endocytosis (particularly phagocytosis). Its loss in unstressed cells impairs endocytosis and causes correspondingly slower growth, while also stimulating mitochondrial respiration. We report here that oxidative stress in Dictyostelium cells inhibits mitochondrial respiration and impairs phagocytosis in an AMPK-dependent manner. This adds to the separate impairment of phagocytosis caused by DJ-1 knockdown. Oxidative stress also combines with DJ-1 loss in an AMPK-dependent manner to impair or exacerbate defects in phototaxis, morphogenesis and growth. It thereby phenocopies mitochondrial dysfunction. These results support a model in which the oxidized but not the reduced form of DJ-1 inhibits AMPK in the cytosol, thereby protecting cells from the adverse consequences of oxidative stress, mitochondrial dysfunction and the resulting AMPK hyperactivity.


2020 ◽  
Vol 13 (9) ◽  
pp. 2903-2914 ◽  
Author(s):  
Andrey Kanygin ◽  
Yuval Milrad ◽  
Chandrasekhar Thummala ◽  
Kiera Reifschneider ◽  
Patricia Baker ◽  
...  

Photosystem I-hydrogenase chimera intercepts electron flow directly from the photosynthetic electron transport chain and directs it to hydrogen production.


2009 ◽  
Vol 192 (5) ◽  
pp. 1410-1415 ◽  
Author(s):  
Minoru Tanigawa ◽  
Tomomitsu Shinohara ◽  
Katsushi Nishimura ◽  
Kumiko Nagata ◽  
Morio Ishizuka ◽  
...  

ABSTRACT Helicobacter pylori is a microaerophilic bacterium associated with gastric inflammation and peptic ulcers. Knowledge of how pathogenic organisms produce energy is important from a therapeutic point of view. We found d-amino acid dehydrogenase-mediated electron transport from d-proline or d-alanine to oxygen via the respiratory chain in H. pylori. Coupling of the electron transport to ATP synthesis was confirmed by using uncoupler reagents. We reconstituted the electron transport chain to demonstrate the electron flow from the d-amino acids to oxygen using the recombinant cytochrome bc 1 complex, cytochrome c-553, and the terminal oxidase cytochrome cbb 3 complex. Upon addition of the recombinant d-amino acid dehydrogenase and d-proline or d-alanine to the reconstituted electron transport system, reduction of cytochrome cbb 3 and oxygen consumption was revealed spectrophotometrically and polarographically, respectively. Among the constituents of H. pylori's electron transport chain, only the cytochrome bc 1 complex had been remained unpurified. Therefore, we cloned and sequenced the H. pylori NCTC 11637 cytochrome bc 1 gene clusters encoding Rieske Fe-S protein, cytochrome b, and cytochrome c 1, with calculated molecular masses of 18 kDa, 47 kDa, and 32 kDa, respectively, and purified the recombinant monomeric protein complex with a molecular mass of 110 kDa by gel filtration. The absorption spectrum of the recombinant cytochrome bc 1 complex showed an α peak at 561 nm with a shoulder at 552 nm.


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