Regulation of Mitochondrial Electron Transport Chain Assembly

Cogliati, Sara; Lorenzi, Isotta; Rigoni, Giovanni; Caicci, Federico; Soriano, María Eugenia

doi:10.1016/j.jmb.2018.09.016

Cited by 70 publications

(50 citation statements)

References 238 publications

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“…The ETC is formed by four complexes (CI-CIV) located in the IMM, whose function is the coupling between the transport of electrons between the complexes and the pumping of protons, creating an electrochemical gradient between the mitochondrial matrix and the intermembrane space, for the synthesis of ATP by the ATP synthase (Cogliati et al, 2018). Complex I or NADH:ubiquinone oxidoreductase accepts the electrons from NADH and delivers it to Complex III through the electron-carrier ubiquinone.…”

Section: The Pathological Interaction Between Complex I Of the Etc Anmentioning

confidence: 99%

“…Complex I or NADH:ubiquinone oxidoreductase accepts the electrons from NADH and delivers it to Complex III through the electron-carrier ubiquinone. It also pumps protons from the mitochondrial matrix to intermembrane space (Busch, 2018;Cogliati et al, 2018).…”

Section: The Pathological Interaction Between Complex I Of the Etc Anmentioning

confidence: 99%

“…Adenosine triphosphate synthase uses the electrochemical gradient generated by the proton pumping of the ETC for the phosphorylation of ADP to form ATP (Cogliati et al, 2018). It has also been shown through PLA assays that α-syn monomers interact with the ATP synthase α-subunit, which suggests that α-syn acts as a regulator of the ATP synthase.…”

Section: The Interaction Of Alpha-synuclein With Atp Synthase Is Depementioning

confidence: 99%

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Alpha-Synuclein Physiology and Pathology: A Perspective on Cellular Structures and Organelles

et al. 2020

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Alpha-synuclein (α-syn) is localized in cellular organelles of most neurons, but many of its physiological functions are only partially understood. α-syn accumulation is associated with Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy as well as other synucleinopathies; however, the exact pathomechanisms that underlie these neurodegenerative diseases remain elusive. In this review, we describe what is known about α-syn function and pathophysiological changes in different cellular structures and organelles, including what is known about its behavior as a prionlike protein. We summarize current knowledge of α-syn and its pathological forms, covering its effect on each organelle, including aggregation and toxicity in different model systems, with special interest on the mitochondria due to its relevance during the apoptotic process of dopaminergic neurons. Moreover, we explore the effect that α-syn exerts by interacting with chromatin remodeling proteins that add or remove histone marks, up-regulate its own expression, and resume the impairment that α-syn induces in vesicular traffic by interacting with the endoplasmic reticulum. We then recapitulate the events that lead to Golgi apparatus fragmentation, caused by the presence of α-syn. Finally, we report the recent findings about the accumulation of α-syn, indirectly produced by the endolysosomal system. In conclusion, many important steps into the understanding of α-syn have been made using in vivo and in vitro models; however, the time is right to start integrating observational studies with mechanistic models of α-syn interactions, in order to look at a more complete picture of the pathophysiological processes underlying α-synucleinopathies.

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Section: The Pathological Interaction Between Complex I Of the Etc Anmentioning

confidence: 99%

Section: The Pathological Interaction Between Complex I Of the Etc Anmentioning

confidence: 99%

Section: The Interaction Of Alpha-synuclein With Atp Synthase Is Depementioning

confidence: 99%

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Alpha-Synuclein Physiology and Pathology: A Perspective on Cellular Structures and Organelles

et al. 2020

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“…Any defects in the core components of the OXPHOS complexes caused by mutations or environmental stress can perturb the assembly and functionality of the oxidative phosphorylation system. In addition, the proper assembly of functional OXPHOS complexes requires a large number of assembly factors 4,5,6 . Blue native polyacrylamide gel electrophoresis (BN-PAGE) is a fundamental technique enabling analysis of intact protein complexes and can be used to study the assembly of OXPHOS complexes.…”

Section: Introductionmentioning

confidence: 99%

Analysis of Mitochondrial Respiratory Chain Complexes in Cultured Human Cells using Blue Native Polyacrylamide Gel Electrophoresis and Immunoblotting

Konovalova

2019

JoVE

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Mitochondrial respiration is performed by oxidative phosphorylation (OXPHOS) complexes within mitochondria. Internal and environmental factors can perturb the assembly and stability of OXPHOS complexes. This protocol describes the analysis of mitochondrial respiratory chain complexes by blue native polyacrylamide gel electrophoresis (BN-PAGE) in application to cultured human cells. First, mitochondria are extracted from the cells using digitonin, then using lauryl maltoside, the intact OXPHOS complexes are isolated from the mitochondrial membranes. The OXPHOS complexes are then resolved by gradient gel electrophoresis in the presence of the negatively charged dye, Coomassie blue, which prevents protein aggregation and ensures electrophoretic mobility of protein complexes towards the cathode. Finally, the OXPHOS complexes are detected by standard immunoblotting. Thus, BN-PAGE is a convenient and inexpensive technique that can be used to evaluate the assembly of entire OXPHOS complexes, in contrast to the basic SDS-PAGE allowing the study of only individual OXPHOS complex subunits.

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“…However, certain mtDNA properties are conserved, e.g. the presence of genes coding for highly hydrophobic and crucial components of the respiratory chain, ribosomal RNAs (rRNAs), and transfer RNAs (tRNAs), which are necessary for protein translation (5). How electron transfer is coupled to proton pumping is a major unresolved question (19).…”

Section: Praca Oryginalnamentioning

confidence: 99%

Analysis of differences in the stability of proteins encoded in mitochondrial DNA of model organisms

Kowal¹,

Bownik²,

Tkaczyk³

et al. 2020

Medycyna Weterynaryjna

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The genetic information on the structure of 37 genes, i.e. 13 respiratory chain proteins, 22 tRNA molecules, and 2 rRNA molecules, is encoded in the mitochondrial genome. Mitochondrial DNA (mtDNA) contains a non-coding region (D-loop), whose length varies among animals. Due to the lack of introns, genes in some organisms overlap, e.g. in humans, the ATP6 and ATP8 genes share 46 nucleotides and the ND4 and ND4L genes share seven nucleotides (2,8). The length of mtDNA is highly variable in different organisms, ranging from yeasts to higher eukaryotes. However, certain mtDNA properties are conserved, e.g. the presence of genes coding for highly hydrophobic and crucial components of the respiratory chain, ribosomal RNAs (rRNAs), and transfer RNAs (tRNAs), which are necessary for protein translation (5). How electron transfer is coupled to proton pumping is a major unresolved question (19). Many metabolic processes, e.g. the Krebs cycle, the urea cycle, or β-oxidation, take place in the mitochondria. Additionally, mitochondria are involved in the regulation of thermogenesis and Ca 2+ ion metabolism and exert an effect on the apoptosis process. However, the main role of mitochondria is generation of high-energy ATP in the process of oxidative phosphorylation (9). The respiratory chain consists of 5 protein complexes: NADH-ubiquinone oxidoreductase, succinate−quinone oxidoreductase, the bc1 complex, cyt c oxidase, and ATP synthase. The complexes are arranged on the internal mitochondrial membrane according to the increasing oxidoreductive potential. The difference in the potentials between the first four complexes facilitates electron transport. It results in generation of energy, which is converted by ATP synthase into high-energy phosphorus bonds (14).Approximately 0.15-2% of electrons that enter the electron transport chain (ETC) can escape the OXPHOS cycle, resulting in the formation of superoxide (22). Increased exposure to this OXPHOS-related superoxide may affect not only the mtDNA located nearby, but also proteins and lipids, resulting in impaired protein Summary The aim of this study was to describe the stability of proteins encoded in mtDNA, which are part of the OXPHOS system, in different model organisms and to define why certain proteins are more prone to be unstable than others. The in silico analyses involved 155 reference sequences of all proteins encoded in the mitochondrial DNA in twelve model organisms representing different phylogenetic groups. The amino acid sequences of the proteins were taken from the GenPept database. The bioinformatic analyses were performed in the ProtParam program. Thirty-eight of the 155 analyzed proteins exhibited instability. The greatest numbers of unstable mitochondrial proteins were detected in H. sapiens and A. mexicanum and the lowest levels were found in C. elegans. ND1 and ATP8 were the most unstable mitochondrial proteins. Proteins COX1 and COX3 did not exhibit instability in the examined group of organisms. The highest instability index values were recorded in the ...

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Regulation of Mitochondrial Electron Transport Chain Assembly

Cited by 70 publications

References 238 publications

Alpha-Synuclein Physiology and Pathology: A Perspective on Cellular Structures and Organelles

Alpha-Synuclein Physiology and Pathology: A Perspective on Cellular Structures and Organelles

Analysis of Mitochondrial Respiratory Chain Complexes in Cultured Human Cells using Blue Native Polyacrylamide Gel Electrophoresis and Immunoblotting

Analysis of differences in the stability of proteins encoded in mitochondrial DNA of model organisms

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