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

Čunátová, Kristýna; Reguera, David; Houštěk, J; Mráček, Tomáš; Pecina, Petr

doi:10.33549/physiolres.934446

Cited by 29 publications

(26 citation statements)

References 122 publications

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“…Of these, COX1 , COX2 , COX3 , CYTB , ATP6 , RPLP1 , and S100A12 have occurred in both youth and adult period. COX1 , COX2 , and COX3 are three subunits of cytochrome c oxidase that may play an important role in the production of vast majority of ATP molecules in mammalian cells ( Čunátová et al, 2020 ). CYTB is involved in electron transport in the mitochondrial respiratory chain ( Seddigh and Darabi 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Transcriptome Analysis of Bovine Rumen Tissue in Three Developmental Stages

Zhang

Cai

et al. 2022

Front. Genet.

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Rumen development is a crucial physiological challenge for ruminants. However, the molecular mechanism regulating rumen development has not been clearly elucidated. In this study, we investigated genes involved in rumen development in 13 rumen tissues from three developmental stages (birth, youth, and adult) using RNA sequencing. We identified that 6,048 genes were differentially expressed among three developmental stages. Using weighted correlation network analysis, we found that 12 modules were significantly associated with developmental stages. Functional annotation and protein–protein interaction (PPI) network analysis revealed that CCNB1, CCNB2, IGF1, IGF2, HMGCL, BDH1, ACAT1, HMGCS2, and CREBBP involved in rumen development. Integrated transcriptome with GWAS information of carcass weight (CW), stomach weight (SW), marbling score (MS), backfat thickness (BFT), ribeye area (REA), and lean meat weight (LMW), we found that upregulated DEGs (fold change 0∼1) in birth–youth comparison were significantly enriched with GWAS signals of MS, downregulated DEGs (fold change >3) were significantly enriched with GWAS signals of SW, and fold change 0∼1 up/downregulated DEGs in birth–adult comparison were significantly enriched with GWAS signals of CW, LMW, REA, and BFT. Furthermore, we found that GWAS signals for CW, LMW, and REA were enriched in turquoise module, and GWAS signals for CW was enriched in lightgreen module. Our study provides novel insights into the molecular mechanism underlying rumen development in cattle and highlights an integrative analysis for illustrating the genetic architecture of beef complex traits.

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Section: Discussionmentioning

confidence: 99%

Transcriptome Analysis of Bovine Rumen Tissue in Three Developmental Stages

Zhang

Cai

et al. 2022

Front. Genet.

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“…As COX4 is an early incorporating subunit [4,13,16,51], impaired assembly of cIV enzyme was expected in COX4I1 and COX4I1/4I2 KO clones. Indeed, native electrophoresis confirmed presence of MT-CO1-containing cIV assembly intermediate, most likely representing a MITRAC complex [20].…”

Section: Discussionmentioning

confidence: 99%

“…Mammalian cIV consists of a catalytic core composed of three mtDNA-encoded subunits: MT-CO1, MT-CO2, and MT-CO3, surrounded by 11 different regulatory subunits encoded in nucleus: COX4, COX5A, COX5B, COX6A, COX6B, COX6C, COX7A, COX7B, COX7C, COX8, and NDUFA4, which is currently also considered as part of the cIV, discovered on the basis of genetic [11] and structural data [12]. Six of the nuclearencoded subunits exist as developmental stage or tissue-specific isoforms [13]. In case of COX4 subunit specifically, alternative isoforms COX4I1 and COX4I2 are expressed by independent genes.…”

Section: Introductionmentioning

confidence: 99%

“…In case of COX4 subunit specifically, alternative isoforms COX4I1 and COX4I2 are expressed by independent genes. COX4I1 represents the ubiquitous isoform, while COX4I2 is mainly lung-specific and its expression is further regulated by oxygen levels [13]. It was recently shown that COX4I2 is necessary for hypoxic pulmonary vasoconstriction [14], and that COX4 isoform exchange may modulate cIV affinity to oxygen [15].…”

Section: Introductionmentioning

confidence: 99%

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Loss of COX4I1 Leads to Combined Respiratory Chain Deficiency and Impaired Mitochondrial Protein Synthesis

Čunátová

Reguera

Vrbacký

et al. 2021

Cells

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The oxidative phosphorylation (OXPHOS) system localized in the inner mitochondrial membrane secures production of the majority of ATP in mammalian organisms. Individual OXPHOS complexes form supramolecular assemblies termed supercomplexes. The complexes are linked not only by their function but also by interdependency of individual complex biogenesis or maintenance. For instance, cytochrome c oxidase (cIV) or cytochrome bc1 complex (cIII) deficiencies affect the level of fully assembled NADH dehydrogenase (cI) in monomeric as well as supercomplex forms. It was hypothesized that cI is affected at the level of enzyme assembly as well as at the level of cI stability and maintenance. However, the true nature of interdependency between cI and cIV is not fully understood yet. We used a HEK293 cellular model where the COX4 subunit was completely knocked out, serving as an ideal system to study interdependency of cI and cIV, as early phases of cIV assembly process were disrupted. Total absence of cIV was accompanied by profound deficiency of cI, documented by decrease in the levels of cI subunits and significantly reduced amount of assembled cI. Supercomplexes assembled from cI, cIII, and cIV were missing in COX4I1 knock-out (KO) due to loss of cIV and decrease in cI amount. Pulse-chase metabolic labeling of mitochondrial DNA (mtDNA)-encoded proteins uncovered a decrease in the translation of cIV and cI subunits. Moreover, partial impairment of mitochondrial protein synthesis correlated with decreased content of mitochondrial ribosomal proteins. In addition, complexome profiling revealed accumulation of cI assembly intermediates, indicating that cI biogenesis, rather than stability, was affected. We propose that attenuation of mitochondrial protein synthesis caused by cIV deficiency represents one of the mechanisms, which may impair biogenesis of cI.

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“…This process is more efficient than anaerobic fermentation [ 23 ]. COX5A and COX6C are both cytochrome c oxidase families that play similar roles associated with cytochrome c oxidase activity [ 24 ]. These subunit proteins of the mitochondrial respiratory chain complex are involved in mitochondrial electron transport and transport from cytochrome c to oxygen.…”

Section: Discussionmentioning

confidence: 99%

Early Heat Exposure Effects on Proteomic Changes of the Broiler Liver under Acute Heat Stress

Kang

Shim

2021

Animals

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As environmental temperatures continue to rise, heat stress (HS) is having a negative effect on the livestock industry. In order to solve this problem, many studies have been conducted to reduce HS. Among them, early heat exposure has been suggested as a method for reducing HS in poultry. In this study, we analyzed proteomics and tried to identify the metabolic mechanisms of early heat exposure on acute HS. A total of 48 chicks were separated into three groups: CC (control groups raised at optimum temperature), CH (raised with CC but exposed acute HS at the 35th day), and HH (raised with CC but exposed early heat at the fifth day and acute HS at the 35th day). After the whole period, liver samples were collected for proteomic analysis. A total of 97 differentially expressed proteins were identified by acute HS. Of these, 62 proteins recovered their expression levels by early heat exposure. We used these 62 proteins to determine the protective effects of early heat exposure. Of the various protein-related terms, we focused on the oxidative phosphorylation, fatty acid metabolism, carbohydrate metabolism, and energy production metabolism. Our findings suggest the possibility of early heat exposure effects in acute HS that may be useful in breeding or management techniques for producing broilers with high heat resistance.

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

Cited by 29 publications

References 122 publications

Transcriptome Analysis of Bovine Rumen Tissue in Three Developmental Stages

Transcriptome Analysis of Bovine Rumen Tissue in Three Developmental Stages

Loss of COX4I1 Leads to Combined Respiratory Chain Deficiency and Impaired Mitochondrial Protein Synthesis

Early Heat Exposure Effects on Proteomic Changes of the Broiler Liver under Acute Heat Stress

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