scholarly journals HIGD-Driven Regulation of Cytochrome c Oxidase Biogenesis and Function

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2620
Author(s):  
Alba Timón-Gómez ◽  
Emma L. Bartley-Dier ◽  
Flavia Fontanesi ◽  
Antoni Barrientos
Keyword(s):  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Current Knowledge ◽  
Chain Complex ◽  
Mitochondrial Respiratory Chain ◽  
Stress Conditions ◽  
Cellular Respiration ◽  
Adaptation To Hypoxia ◽  
Mitochondrial Respiratory Chain Complex ◽  
And Function

The biogenesis and function of eukaryotic cytochrome c oxidase or mitochondrial respiratory chain complex IV (CIV) undergo several levels of regulation to adapt to changing environmental conditions. Adaptation to hypoxia and oxidative stress involves CIV subunit isoform switch, changes in phosphorylation status, and modulation of CIV assembly and enzymatic activity by interacting factors. The latter include the Hypoxia Inducible Gene Domain (HIGD) family yeast respiratory supercomplex factors 1 and 2 (Rcf1 and Rcf2) and two mammalian homologs of Rcf1, the proteins HIGD1A and HIGD2A. Whereas Rcf1 and Rcf2 are expressed constitutively, expression of HIGD1A and HIGD2A is induced under stress conditions, such as hypoxia and/or low glucose levels. In both systems, the HIGD proteins localize in the mitochondrial inner membrane and play a role in the biogenesis of CIV as a free unit or as part as respiratory supercomplexes. Notably, they remain bound to assembled CIV and, by modulating its activity, regulate cellular respiration. Here, we will describe the current knowledge regarding the specific and overlapping roles of the several HIGD proteins in physiological and stress conditions.

New perspectives on the assembly process of mitochondrial respiratory chain complex cytochrome c oxidase

Mitochondrion ◽  
2002 ◽  
Vol 2 (1-2) ◽  
pp. 117-128 ◽  
Author(s):  
Cristina Ugalde ◽  
Marieke J.H Coenen ◽  
Murtada H Farhoud ◽  
Stefanie Gilinsky ◽  
Werner J.H Koopman ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Respiratory Chain ◽  
Chain Complex ◽  
Mitochondrial Respiratory Chain ◽  
Assembly Process ◽  
Respiratory Chain Complex ◽  
Mitochondrial Respiratory Chain Complex ◽  
Mitochondrial Respiratory

scholarly journals The function of Scox in glial cells is essential for locomotive ability in Drosophila

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ryosuke Kowada ◽  
Atsushi Kodani ◽  
Hiroyuki Ida ◽  
Masamitsu Yamaguchi ◽  
Im-Soon Lee ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Glial Cell ◽  
Glial Cells ◽  
Neurodegenerative Disorder ◽  
Chain Complex ◽  
Mitochondrial Morphology ◽  
Common Symptom ◽  
Mitochondrial Respiratory Chain Complex ◽  
And Function

AbstractSynthesis of cytochrome c oxidase (Scox) is a Drosophila homolog of human SCO2 encoding a metallochaperone that transports copper to cytochrome c, and is an essential protein for the assembly of cytochrome c oxidase in the mitochondrial respiratory chain complex. SCO2 is highly conserved in a wide variety of species across prokaryotes and eukaryotes, and mutations in SCO2 are known to cause mitochondrial diseases such as fatal infantile cardioencephalomyopathy, Leigh syndrome, and Charcot-Marie-Tooth disease, a neurodegenerative disorder. These diseases have a common symptom of locomotive dysfunction. However, the mechanisms of their pathogenesis remain unknown, and no fundamental medications or therapies have been established for these diseases. In this study, we demonstrated that the glial cell-specific knockdown of Scox perturbs the mitochondrial morphology and function, and locomotive behavior in Drosophila. In addition, the morphology and function of synapses were impaired in the glial cell-specific Scox knockdown. Furthermore, Scox knockdown in ensheathing glia, one type of glial cell in Drosophila, resulted in larval and adult locomotive dysfunction. This study suggests that the impairment of Scox in glial cells in the Drosophila CNS mimics the pathological phenotypes observed by mutations in the SCO2 gene in humans.

scholarly journals Regulation of Mitochondrial Respiratory Chain Complex Levels, Organization, and Function by Arginyltransferase 1

2020 ◽  
Vol 8 ◽  
Author(s):  
Chunhua Jiang ◽  
Balaji T. Moorthy ◽  
Devang M. Patel ◽  
Akhilesh Kumar ◽  
William M. Morgan ◽  
...  
Keyword(s):  
Respiratory Chain ◽  
Chain Complex ◽  
Mitochondrial Respiratory Chain ◽  
Underlying Mechanism ◽  
Metabolic Effects ◽  
Respiratory Chain Complexes ◽  
Mitochondrial Respiratory Chain Complex ◽  
Human Disorders ◽  
And Function ◽  
Alpha Proteobacteria

Arginyltransferase 1 (ATE1) is an evolutionary-conserved eukaryotic protein that localizes to the cytosol and nucleus. It is the only known enzyme in metazoans and fungi that catalyzes posttranslational arginylation. Lack of arginylation has been linked to an array of human disorders, including cancer, by altering the response to stress and the regulation of metabolism and apoptosis. Although mitochondria play relevant roles in these processes in health and disease, a causal relationship between ATE1 activity and mitochondrial biology has yet to be established. Here, we report a phylogenetic analysis that traces the roots of ATE1 to alpha-proteobacteria, the mitochondrion microbial ancestor. We then demonstrate that a small fraction of ATE1 localizes within mitochondria. Furthermore, the absence of ATE1 influences the levels, organization, and function of respiratory chain complexes in mouse cells. Specifically, ATE1-KO mouse embryonic fibroblasts have increased levels of respiratory supercomplexes I+III2+IVn. However, they have decreased mitochondrial respiration owing to severely lowered complex II levels, which leads to accumulation of succinate and downstream metabolic effects. Taken together, our findings establish a novel pathway for mitochondrial function regulation that might explain ATE1-dependent effects in various disease conditions, including cancer and aging, in which metabolic shifts are part of the pathogenic or deleterious underlying mechanism.

scholarly journals The Mitochondrial Acyl-carrier Protein Interaction Network Highlights Important Roles for LYRM Family Members in Complex I and Mitoribosome Assembly

2019 ◽  
Vol 19 (1) ◽  
pp. 65-77 ◽  
Author(s):  
Marris G. Dibley ◽  
Luke E. Formosa ◽  
Baobei Lyu ◽  
Boris Reljic ◽  
Dylan McGann ◽  
...  
Keyword(s):  
Complex I ◽  
Acyl Carrier Protein ◽  
Chain Complex ◽  
Interaction Network ◽  
Mitochondrial Respiratory Chain ◽  
Cellular Respiration ◽  
Carrier Protein ◽  
Post Translational Modification ◽  
Mitochondrial Respiratory Chain Complex ◽  
Mitochondrial Ribosome

NDUFAB1 is the mitochondrial acyl carrier protein (ACP) essential for cell viability. Through its pantetheine-4′-phosphate post-translational modification, NDUFAB1 interacts with members of the leucine-tyrosine-arginine motif (LYRM) protein family. Although several LYRM proteins have been described to participate in a variety of defined processes, the functions of others remain either partially or entirely unknown. We profiled the interaction network of NDUFAB1 to reveal associations with 9 known LYRM proteins as well as more than 20 other proteins involved in mitochondrial respiratory chain complex and mitochondrial ribosome assembly. Subsequent knockout and interaction network studies in human cells revealed the LYRM member AltMiD51 to be important for optimal assembly of the large mitoribosome subunit, consistent with recent structural studies. In addition, we used proteomics coupled with topographical heat-mapping to reveal that knockout of LYRM2 impairs assembly of the NADH-dehydrogenase module of complex I, leading to defects in cellular respiration. Together, this work adds to the catalogue of functions executed by LYRM family of proteins in building mitochondrial complexes and emphasizes the common and essential role of NDUFAB1 as a protagonist in mitochondrial metabolism.

scholarly journals Role of cytochrome c oxidase nuclear-encoded subunits in health and disease

2020 ◽  
pp. 947-965
Author(s):  
K Čunátová ◽  
D Pajuelo Reguera ◽  
J Houštěk ◽  
T Mráček ◽  
P Pecina
Keyword(s):  
Electron Transport ◽  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Mammalian Cells ◽  
Current Knowledge ◽  
Fine Tuning ◽  
Transport Chain ◽  
Associated Proteins ◽  
And Function ◽  
Structural Levels

Cytochrome c oxidase (COX), the terminal enzyme of mitochondrial electron transport chain, couples electron transport to oxygen with generation of proton gradient indispensable for the production of vast majority of ATP molecules in mammalian cells. The review summarizes current knowledge of COX structure and function of nuclear-encoded COX subunits, which may modulate enzyme activity according to various conditions. Moreover, some nuclear-encoded subunits posess tissue-specific and development-specific isoforms, possibly enabling fine-tuning of COX function in individual tissues. The importance of nuclear-encoded subunits is emphasized by recently discovered pathogenic mutations in patients with severe mitopathies. In addition, proteins substoichiometrically associated with COX were found to contribute to COX activity regulation and stabilization of the respiratory supercomplexes. Based on the summarized data, a model of three levels of quaternary COX structure is postulated. Individual structural levels correspond to subunits of the i) catalytic center, ii) nuclear-encoded stoichiometric subunits and iii) associated proteins, which may constitute several forms of COX with varying composition and differentially regulated function.

Dietary dimethylglycine sodium salt supplementation improves growth performance, redox status, and skeletal muscle function of intrauterine growth restriction weaned piglets

2021 ◽  
Author(s):  
Kaiwen Bai ◽  
Luyi Jiang ◽  
Qiming Li ◽  
Jingfei Zhang ◽  
Lili Zhang ◽  
...  
Keyword(s):  
Growth Performance ◽  
Mitochondrial Function ◽  
Chain Complex ◽  
Basal Diet ◽  
Mitochondrial Respiratory Chain ◽  
Redox Status ◽  
Weaned Piglets ◽  
Complex Activity ◽  
Mitochondrial Respiratory Chain Complex ◽  
Intrauterine Growth

Abstract Few studies have focused on the role of dimethylglycine sodium salt (DMG-Na) in protecting the redox status of skeletal muscle, although it is reported to be beneficial in animal husbandry. This study investigated the beneficial effects of DMG-Na on the growth performance, longissimus dorsi muscle (LM) redox status, and mitochondrial function in weaning piglets that were intrauterine growth restricted (IUGR). Ten normal birth weight (NBW) newborn piglets (1.53 ± 0.04 kg) and 20 IUGR newborn piglets (0.76 ± 0.06 kg) from ten sows were obtained. All piglets were weaned at 21 days of age and allocated to three groups with ten replicates per group: NBW-weaned piglets fed a common basal diet (N); IUGR weaned piglets fed a common basal diet (I); IUGR weaned piglets fed a common basal diet supplemented with 0.1% DMG-Na (ID). They were slaughtered at 49 days of age to collect the serum and LM samples. Compared with the N group, the growth performance, LM structure, serum, and, within the LM, mitochondrial redox status, mitochondrial respiratory chain complex activity, energy metabolites, redox status-related, cell adhesion-related, and mitochondrial function-related gene expression, and protein expression deteriorated in group I (P < 0.05). The ID group showed improved growth performance, LM structure, serum, and, within the LM, mitochondrial redox status, mitochondrial respiratory chain complex activity, energy metabolites, redox status-related, cell adhesion-related, and mitochondrial function-related gene expression, and protein expression compared with those in the I group (P < 0.05). The above results indicated that the DMG-Na treatment could improve the LM redox status and mitochondrial function in IUGR weaned piglets via the Nuclear factor erythroid 2-related factor 2 (Nrf2)/ Sirtuin 1 (SIRT1)/ Peroxisome proliferator-activated receptorγcoactivator-1α (PGC1α) network, thus improving their growth performance.

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