Mitochondrial respiratory supercomplexes in mammalian cells: structural versus functional role

Javadov, Sabzali; Jang, Sehwan; Chapa‐Dubocq, Xavier R.; Khuchua, Zaza; Camara, Amadou K.S.

doi:10.1007/s00109-020-02004-8

Cited by 42 publications

(36 citation statements)

References 147 publications

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“…They have also been suggested to play a role in preventing random protein aggregation in the protein rich inner mitochondrial membrane. However, all these suggested roles have been challenged and no clear consensus has emerged 84 . While our data suggest that the free form respiratory complexes are the dominant species in P. falciparum mitochondria, it is hard to estimate whether this balance is representative of the in vivo abundances and what impact solubilization and electrophoresis procedures have on stability of the supercomplexes.…”

Section: Discussionmentioning

confidence: 99%

Composition and stage dynamics of mitochondrial complexes in Plasmodium falciparum

et al. 2021

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Our current understanding of mitochondrial functioning is largely restricted to traditional model organisms, which only represent a fraction of eukaryotic diversity. The unusual mitochondrion of malaria parasites is a validated drug target but remains poorly understood. Here, we apply complexome profiling to map the inventory of protein complexes across the pathogenic asexual blood stages and the transmissible gametocyte stages of Plasmodium falciparum. We identify remarkably divergent composition and clade-specific additions of all respiratory chain complexes. Furthermore, we show that respiratory chain complex components and linked metabolic pathways are up to 40-fold more prevalent in gametocytes, while glycolytic enzymes are substantially reduced. Underlining this functional switch, we find that cristae are exclusively present in gametocytes. Leveraging these divergent properties and stage dynamics for drug development presents an attractive opportunity to discover novel classes of antimalarials and increase our repertoire of gametocytocidal drugs.

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Section: Discussionmentioning

confidence: 99%

Composition and stage dynamics of mitochondrial complexes in Plasmodium falciparum

et al. 2021

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“…We detected only one positive selection gene ( ND5 gene) using the branch‐site model. The ND5 gene is involved in the regulation of electron transfer in the respiratory chain, which provides necessary energy for vertebrate activity (Brandt, 2006; Javadov et al, 2021; Sousa et al, 2018). We suggest that the ND5 gene is responsible for high‐altitude adaptation in vertebrate.…”

Section: Discussionmentioning

confidence: 99%

High‐altitude adaptation in vertebrates as revealed by mitochondrial genome analyses

Wang

Zhou

et al. 2021

Ecology and Evolution

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The high‐altitude environment may drive vertebrate evolution in a certain way, and vertebrates living in different altitude environments might have different energy requirements. We hypothesized that the high‐altitude environment might impose different influences on vertebrate mitochondrial genomes (mtDNA). We used selection pressure analyses and PIC (phylogenetic independent contrasts) analysis to detect the evolutionary rate of vertebrate mtDNA protein‐coding genes (PCGs) from different altitudes. The results showed that the ratio of nonsynonymous/synonymous substitutions (dN/dS) in the mtDNA PCGs was significantly higher in high‐altitude vertebrates than in low‐altitude vertebrates. The seven rapidly evolving genes were shared by the high‐altitude vertebrates, and only one positive selection gene (ND5 gene) was detected in the high‐altitude vertebrates. Our results suggest the mtDNA evolutionary rate in high‐altitude vertebrates was higher than in low‐altitude vertebrates as their evolution requires more energy in a high‐altitude environment. Our study demonstrates the high‐altitude environment (low atmospheric O2 levels) drives vertebrate evolution in mtDNA PCGs.

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“…The random collision model was accepted by most researchers in this field. Nevertheless, the accumulation of further experimental evidence obtained with newly developed Life 2021, 11, 242 4 of 53 techniques has led to the proposal of a different model of supramolecular organization based upon specific interactions between individual respiratory complexes [28].…”

Section: Organization Of the Respiratory Chain: Historical Outlinementioning

confidence: 99%

Molecular and Supramolecular Structure of the Mitochondrial Oxidative Phosphorylation System: Implications for Pathology

Nesci

Trombetti

Pagliarani

et al. 2021

Life

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Under aerobic conditions, mitochondrial oxidative phosphorylation (OXPHOS) converts the energy released by nutrient oxidation into ATP, the currency of living organisms. The whole biochemical machinery is hosted by the inner mitochondrial membrane (mtIM) where the protonmotive force built by respiratory complexes, dynamically assembled as super-complexes, allows the F1FO-ATP synthase to make ATP from ADP + Pi. Recently mitochondria emerged not only as cell powerhouses, but also as signaling hubs by way of reactive oxygen species (ROS) production. However, when ROS removal systems and/or OXPHOS constituents are defective, the physiological ROS generation can cause ROS imbalance and oxidative stress, which in turn damages cell components. Moreover, the morphology of mitochondria rules cell fate and the formation of the mitochondrial permeability transition pore in the mtIM, which, most likely with the F1FO-ATP synthase contribution, permeabilizes mitochondria and leads to cell death. As the multiple mitochondrial functions are mutually interconnected, changes in protein composition by mutations or in supercomplex assembly and/or in membrane structures often generate a dysfunctional cascade and lead to life-incompatible diseases or severe syndromes. The known structural/functional changes in mitochondrial proteins and structures, which impact mitochondrial bioenergetics because of an impaired or defective energy transduction system, here reviewed, constitute the main biochemical damage in a variety of genetic and age-related diseases.

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Mitochondrial respiratory supercomplexes in mammalian cells: structural versus functional role

Cited by 42 publications

References 147 publications

Composition and stage dynamics of mitochondrial complexes in Plasmodium falciparum

Composition and stage dynamics of mitochondrial complexes in Plasmodium falciparum

High‐altitude adaptation in vertebrates as revealed by mitochondrial genome analyses

Molecular and Supramolecular Structure of the Mitochondrial Oxidative Phosphorylation System: Implications for Pathology

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