chchd2

OBJECTIVE: Intra-amniotic inflammation (IAI), associated with either microbe (infection) or danger signals (sterile), plays a major role in the pathophysiology of preterm labor and delivery. Coiled-Coil-Helix-Coiled-Coil-Helix Domain Containing 2 (CHCHD2) [also known as Mitochondrial Nuclear Retrograde Regulator 1 (MNRR1)], a mitochondrial protein involved in oxidative phosphorylation and cell survival, is capable of sensing tissue hypoxia and inflammatory signaling. The ability to maintain an appropriate energy balance at the cellular level while adapting to environmental stress is essential for the survival of an organism...

Certain long non-coding RNAs (lncRNAs) are known to contain small open reading frames that can be translated. Here we describe a much larger 25 kDa human protein, "<u>R</u>ibosomal <u>I</u>GS <u>E</u>ncoded <u>P</u>rotein" (RIEP), that remarkably is encoded by the well-characterized RNA polymerase (RNAP) II-transcribed nucleolar "promoter and pre-rRNA antisense" lncRNA ( PAPAS ). Strikingly, RIEP, which is conserved throughout primates but not found in other species, predominantly localizes to the nucleolus as well as mitochondria, but both exogenously expressed and endogenous RIEP increase in the nuclear and perinuclear regions upon heat shock (HS)...

Mutations in CHCHD10 and CHCHD2, encoding two paralogous mitochondrial proteins, have been identified in cases of amyotrophic lateral sclerosis, frontotemporal lobar degeneration, and Parkinson's disease. Their role in disease is unclear, though both have been linked to mitochondrial respiration and mitochondrial stress responses. Here, we investigated the biological roles of these proteins during vertebrate development using knockout (KO) models in zebrafish. We demonstrate that loss of either or both proteins leads to motor impairment, reduced survival and compromised neuromuscular junction integrity in larval zebrafish...

INTRODUCTION: Although genetic factors are known to play a role in the pathogenesis of Parkinson's disease (PD), true prevalence of familial PD is unknown. We conducted this pilot study to identify genes implicated in familial Parkinson's disease among Filipinos. METHODS: Eighteen Filipino patients belonging to 11 families with personal and family history of PD underwent thorough evaluation by movement disorders specialists. Samples were analyzed in Juntendo University, Tokyo, Japan...

Cancer progression requires the acquisition of mechanisms that support proliferative potential and metastatic capacity. MNRR1 (also CHCHD2, PARK22, AAG10) is a bi-organellar protein that in the mitochondria can bind to Bcl-xL to enhance its anti-apoptotic function, or to respiratory chain complex IV (COX IV) to increase mitochondrial respiration. In the nucleus, it can act as a transcription factor and promote the expression of genes involved in mitochondrial biogenesis, migration, and cellular stress response...

Nonalcoholic steatohepatitis (NASH) is closely related to liver fibrosis. The role of coiled-coil-helix-coiled-coil-helix domain-containing 2 (CHCHD2) in NASH remains unknown. CHCHD2's functions as a transcription factor have received much less attention than those in mitochondria. Herein, we systematically characterized the role of CHCHD2 as a transcription factor by chromatin immunoprecipitation sequencing and found its target genes were enriched in nonalcoholic fatty liver disease (NAFLD). Overall, CHCHD2 expression was found to be increased in the livers of patients with NAFLD and those of NASH mice...

BACKGROUND: Nonalcoholic fatty liver disease affects about 24% of the world's population and may progress to nonalcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma (HCC). While more common in those that are obese, NASH-HCC can develop in lean individuals. The mechanisms by which HCC develops and the role of epigenetic changes in the context of obesity and normal weight are not well understood. METHODS: In this study, we used previously generated mouse models of lean and obese HCC using a choline deficient/high trans-fat/fructose/cholesterol diet and a choline supplemented/high trans-fat/fructose/cholesterol diet, respectively, to evaluate methylation differences in HCC progression in lean versus obese mice...

The p.Thr61Ile (p.T61I) mutation in coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2) was deemed a causative factor in Parkinson's disease (PD). However, the pathomechanism of the CHCHD2 p.T61I mutation in PD remains unclear. Few existing mouse models of CHCHD2-related PD completely reproduce the features of PD, and no transgenic or knock-in (KI) mouse models of CHCHD2 mutations have been reported. In the present study, we generated a novel CHCHD2 p.T61I KI mouse model, which exhibited accelerated mortality, progressive motor deficits, and dopaminergic (DA) neurons loss with age, accompanied by the accumulation and aggregation of α-synuclein and p-α-synuclein in the brains of the mutant mice...

Coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2) and Coiled-coil-helix-coiled-coil-helix domain containing 10 (CHCHD10) are mitochondrial proteins that are thought to be genes which duplicated during evolution and are the causative genes for Parkinson's disease and amyotrophic lateral sclerosis/frontotemporal lobe dementia, respectively. CHCHD2 forms a heterodimer with CHCHD10 and a homodimer with itself, both of which work together within the mitochondria. Various pathogenic and disease-risk variants have been identified; however, how these mutations cause neurodegeneration in specific diseases remains a mystery...

CHCHD2 and CHCHD10 are homolog mitochondrial proteins that play key roles in the neurological, cardiovascular, and reproductive systems. They are also involved in the mitochondrial metabolic process. Although previous research has concentrated on their functions within mitochondria, their functions within apoptosis, synaptic plasticity, cell migration as well as lipid metabolism remain to be concluded. The review highlights the different roles played by CHCHD2 and/or CHCHD10 binding to various target proteins (such as OPA-1, OMA-1, PINK, and TDP43) and reveals their non-negligible effects in cognitive impairments and motor neuron diseases...

CHCHD2 mutations have been reported to cause Parkinson's disease (PD) by a loss of function in mitochondria. Most reported mutations, however, were missense, which was not the perfect model for a study of haploinsufficiency. Here, a truncated mutation, CHCHD2 p.Pro53Alafs*38, was identified in one familial early-onset PD patient. We generated a human-induced pluripotent stem cell (iPSC) line WCHSCUi001-A from this patient. The generated iPSCs resembled human embryonic stem cells, expressed pluripotency markers, exhibited a normal karyotype and could be differentiated into three germ layers in vitro...

Chaperonin containing TCP1 subunit 6A (CCT6A) and coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2) are located at the chromosome 7p11 region proximal to epidermal growth factor receptor (EGFR). However, the amplifications, expressions, and the prognostic effects of CCT6A and CHCDH2 in lung adenocarcinoma (LUAD) are unclear. Here, using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets, we found that CCT6A was coamplified and coexpressed with EGFR in LUAD patients. CCT6A amplification was correlated with the unfavorable outcomes of LUAD...

Amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD) patients show a higher prevalence of Lewy body disease than the general population. Additionally, parkinsonian features were found in about 30% of ALS patients. We aimed to explore the frequency of Parkinson's disease (PD)-causative genes in ALS patients, compared to AD and healthy controls (HCs). We used next-generation sequencing multigene panels by analyzing SNCA , LRRK2 , PINK1 , PARK2 , PARK7 , SYNJ1 , CHCHD2 , PLA2G6 , GCH1 , ATP13A2 , DNAJC6 and FBXO genes...

BACKGROUND: Recent genetic progress has shown many causative/risk genes linked to Parkinson's disease (PD), mainly in patients of European ancestry. The study aimed to investigate the PD-related genes and determine the mutational spectrum of early-onset PD in ethnic Chinese. METHODS: In this study, whole-exome sequencing and/or gene dosage analysis were performed in 704 early-onset PD (EOPD) patients (onset age ≤ 45 years) and 1866 controls. Twenty-six PD-related genes and 20 other genes linked to neurodegenerative and lysosome diseases were analyzed...

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's dementia. Mitochondrial dysfunction is involved in the pathology of PD. Coiled-coil-helix-coiled-coil-helix domain-containing 2 (CHCHD2) was identified as associated with autosomal dominant PD. However, the mechanism of CHCHD2 in PD remains unclear. METHODS: Short hairpin RNA (ShRNA)-mediated CHCHD2 knockdown or lentivirus-mediated CHCHD2 overexpression was performed to investigate the impact of CHCHD2 on mitochondrial morphology and function in neuronal tumor cell lines represented with human neuroblastoma (SHSY5Y) and HeLa cells...

Many different intrinsically disordered proteins and proteins with intrinsically disordered regions are associated with neurodegenerative diseases. These types of proteins including amyloid-β, tau, α-synuclein, CHCHD2, CHCHD10, and G-protein coupled receptors are increasingly becoming evaluated as potential drug targets in the pharmaceutical-based treatment approaches. Here, we focus on the neurobiology of this class of proteins, which lie at the center of numerous neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases, Huntington's disease, amyotrophic lateral sclerosis, frontotemporal dementia, Charcot-Marie-Tooth diseases, spinal muscular atrophy, and mitochondrial myopathy...

Coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2) is a mitochondrial protein that plays important roles in cristae structure, oxidative phosphorylation, and apoptosis. Multiple mutations in CHCHD2 have been associated with Lewy body disorders (LBDs), such as Parkinson's disease (PD) and dementia with Lewy bodies (DLB), with the CHCHD2-T61I mutation being the most widely studied. However, at present, only CHCHD2 knockout or CHCHD2/CHCHD10 double knockout mouse models have been investigated. They do not recapitulate the pathology seen in patients with CHCHD2 mutations...

Background: Genetic factors play an important role in the pathogenesis of early-onset Parkinson's disease (EOPD). To date, more than 20 pathogenic genes associated with Parkinson's disease (PD) have been identified. This study aims to explore the mutation spectrum of EOPD and the clinical characteristics of mutation carriers in eastern China. Methods: We recruited 155 unrelated EOPD patients, including 8 familial and 147 sporadic EOPD (age at onset ≤ 50 years)...

Purpose: This study aimed to construct a prognostic signature consisting of immune-related RNA-binding proteins (RBPs) to predict the prognosis of patients with head and neck squamous cell carcinoma (HNSCC) effectively. Methods: The transcriptome and clinical data of HNSCC were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. First, we ascertained the immunological differences in HNSCC, through single-sample gene set enrichment analysis, stromal and immune cells in malignant tumor tissues using expression data (ESTIMATE), and cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) deconvolution algorithm...

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