Homozygous missense mutation in UQCRC2 associated with severe encephalomyopathy, mitochondrial complex III assembly defect and activation of mitochondrial protein quality control

D, Burská; Stibůrek, Lukáš; Křížová, Jana; Vanišová, Marie; Martínek, Václav; Sladkova, Jana; Zámečnı́k, Josef; Honzík, Tomáš; Zeman, Jiří; Hansı́ková, Hana; Tesařová, Markéta

doi:10.1016/j.bbadis.2021.166147

Cited by 16 publications

(17 citation statements)

References 72 publications

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“…The first four genes have been introduced above. UQCRC1 and UQCRFS1 are one of the subunits of complex III ( 41 ) in the inner mitochondrial membrane, and their enrichment pathways were also the same as that of UQCR10. CDK1 is a kind of cyclin-dependent kinases (CDKs), which are serine/threonine kinases whose activity depends on a regulatory subunit—a cyclin.…”

Section: Discussionmentioning

confidence: 90%

“…Combined with the lncRNA- mRNA regulatory network ( Figure 4 ), we can find that both NDUFAB1 and NDUFS7 have a targeting relationship with lncRNA TCONS_00061389, which is also in the first 10 lncRNAs of S14vsS20. UQCR10 is an important component of complex III ( 41 ). It was enriched in three pathways cardiac muscle contraction, oxidative phosphorylation and metabolic pathways ( Figure 6 ).…”

Section: Discussionmentioning

confidence: 99%

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Transcriptome Integration Analysis at Different Embryonic Ages Reveals Key lncRNAs and mRNAs for Chicken Skeletal Muscle

Zhou²,

Zhang³

et al. 2022

Front. Vet. Sci.

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The growth and development of skeletal muscle at embryonic stages are vital and it directly affects the growth performance of chickens. Long non-coding RNA (lncRNA) plays an important role in this process. In the experiment, we collected the leg muscles of fast- and slow-growing Bian chickens both at 14- and 20-day embryo ages (14E and 20E) for RNA-seq. Finally, 292 and 347 differentially expressed (DE) lncRNAs were identified in F14vsF20 and S14vsS20, and 1,295 and 1,560 DE mRNAs were also screened, respectively. Then we constructed lncRNA-mRNA networks for the two groups, respectively, and found that 6 of the top 10 lncRNAs ranked with degree are same. GO analysis showed that 12 of the top 20 terms were same in the two comparison groups and most of them were related to energy metabolisms, such as cellular respiration and aerobic respiration. KEGG enrichment revealed that up to 16 pathways of the top 20 in F14vsF20 were same as that of S14vsS20 and most of them were related to growth, including citrate cycle (TCA cycle) and oxidative phosphorylation. Further analysis showed that there were 602 and 102 same DE mRNAs and DE lncRNAs between the two comparison groups. We then identified 442 lncRNA-mRNA pairs, including 201 mRNAs and 32 lncRNAs. Protein-Protein Interactions (PPI) network was predicted for the 201 mRNAs and three core networks were obtained using the plug-in MCODE of Cytoscape. Then the function of genes in the three core networks was further analyzed with ClueGo and they were mainly enriched in six groups of biological processes. On this basis, combined with KEGG pathways and lncRNA-mRNA networks, we identified several candidate lncRNAs and mRNAs. Among them, lncRNAs mainly include TCONS_00061389, TCONS_00025495, TCONS_00017622, TCONS_00216258 and TCONS_00084223, and mRNAs include PLK1, BUB1, TTK, NDUFS7 NDUFAB1, PDHA1, CDK1, SDHA, ACO2 and MDH1. The results would provide a foundation for further experiments on the role of lncRNAs in the regulation of muscle development. And it could also contribute to further clarify the regulatory mechanism of chicken skeletal muscle.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Transcriptome Integration Analysis at Different Embryonic Ages Reveals Key lncRNAs and mRNAs for Chicken Skeletal Muscle

Zhou²,

Zhang³

et al. 2022

Front. Vet. Sci.

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“…UQCRC1, UQCRFS1, and MRPL15 are also mitochondrial complex subunits with a prominent role in mitochondrial metabolism 54 – 56 . Particularly, evidence from in vitro studies has shown that overexpression of UQCRC1 leads to higher phosphorylation of the PI3K/Akt signaling pathway in parallel with cell apoptosis decline via decreased caspase-3 activation 57 .…”

Section: Discussionmentioning

confidence: 99%

“…Specifically, decreased UQCRC1 content in skeletal muscle is linked with reduced mitochondrial oxidative capacity in a peroxisome proliferator-activated receptor gamma co-activator 1-alpha-dependent manner, leading to muscle fibre atrophy 62 . Moreover, dysfunctions in UQCRC1 and UQCRFS1 are associated with reduced mitochondrial complex III respiratory chain and brain mitochondrial content 56 , leading to disruption of brain mitochondrial bioenergetics 63 – 65 . Indeed, dysregulation of UQCRC1 and UQCRFS1 are linked with prefrontal cortex degeneration 66 , as shown in blood tissue of patients with AD 67 , 68 , while recently, a link between MRPL15 with AD diagnosis was revealed 69 .…”

Section: Discussionmentioning

confidence: 99%

Altered mitochondrial microenvironment at the spotlight of musculoskeletal aging and Alzheimer’s disease

Giannos

Prokopidis

Raleigh

et al. 2022

Sci Rep

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Emerging evidence has linked Alzheimer’s disease (AD) onset with musculoskeletal aging via a muscle-brain crosstalk mediated by dysregulation of the mitochondrial microenvironment. This study investigated gene expression profiles from skeletal muscle tissues of older healthy adults to identify potential gene biomarkers whose dysregulated expression and protein interactome were involved in AD. Screening of the literature resulted in 12 relevant microarray datasets (GSE25941, GSE28392, GSE28422, GSE47881, GSE47969, GSE59880) in musculoskeletal aging and (GSE4757, GSE5281, GSE16759, GSE28146, GSE48350, GSE84422) in AD. Retrieved differentially expressed genes (DEGs) were used to construct two unique protein–protein interaction networks and clustering gene modules were identified. Overlapping module DEGs in the musculoskeletal aging and AD networks were ranked based on 11 topological algorithms and the five highest-ranked ones were considered as hub genes. The analysis revealed that the dysregulated expression of the mitochondrial microenvironment genes, NDUFAB1, UQCRC1, UQCRFS1, NDUFS3, and MRPL15, overlapped between both musculoskeletal aging and AD networks. Thus, these genes may have a potential role as markers of AD occurrence in musculoskeletal aging. Human studies are warranted to evaluate the functional role and prognostic value of these genes in aging populations with sarcopenia and AD.

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“…This defect in OXPHOS, especially for CIII, causes severe neurological disorders characterized by severe psychomotor retardation and global dementia with defects in verbal and expressive communication skills (Barel et al, 2008 ). Another homozygous missense mutation (p.G222A) in one core subunit UQCRC2, which plays an important role in CIII dimerization during the early period of the CIII assembly (Stephan and Ott, 2020 ), also causes neurological disorders, presenting with severe encephalomyopathy, paleocerebellar symptomatology, delay in motoric and cognitive functions (Burska et al, 2021 ). Additionally, one girl with two homozygous missense variations in UQCC2 leads to a severe reduction of UQCC2 protein, a key assembly factor that regulates MT-CYB expression and subsequent complex III assembly (Tucker et al, 2013 ).…”

Section: Dysregulation Of Mitochondrial Bioenergeticsmentioning

confidence: 99%

Mitochondrial protein dysfunction in pathogenesis of neurological diseases

Wang

Zhou

et al. 2022

Front. Mol. Neurosci.

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Mitochondria are essential organelles for neuronal function and cell survival. Besides the well-known bioenergetics, additional mitochondrial roles in calcium signaling, lipid biogenesis, regulation of reactive oxygen species, and apoptosis are pivotal in diverse cellular processes. The mitochondrial proteome encompasses about 1,500 proteins encoded by both the nuclear DNA and the maternally inherited mitochondrial DNA. Mutations in the nuclear or mitochondrial genome, or combinations of both, can result in mitochondrial protein deficiencies and mitochondrial malfunction. Therefore, mitochondrial quality control by proteins involved in various surveillance mechanisms is critical for neuronal integrity and viability. Abnormal proteins involved in mitochondrial bioenergetics, dynamics, mitophagy, import machinery, ion channels, and mitochondrial DNA maintenance have been linked to the pathogenesis of a number of neurological diseases. The goal of this review is to give an overview of these pathways and to summarize the interconnections between mitochondrial protein dysfunction and neurological diseases.

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Homozygous missense mutation in UQCRC2 associated with severe encephalomyopathy, mitochondrial complex III assembly defect and activation of mitochondrial protein quality control

Cited by 16 publications

References 72 publications

Transcriptome Integration Analysis at Different Embryonic Ages Reveals Key lncRNAs and mRNAs for Chicken Skeletal Muscle

Transcriptome Integration Analysis at Different Embryonic Ages Reveals Key lncRNAs and mRNAs for Chicken Skeletal Muscle

Altered mitochondrial microenvironment at the spotlight of musculoskeletal aging and Alzheimer’s disease

Mitochondrial protein dysfunction in pathogenesis of neurological diseases

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