HCCS

Last update 08 May 2025

Basic Info

Synonyms

CCHL, Cytochrome c-type heme lyase, HCCS

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Introduction

Lyase that catalyzes the covalent linking of the heme group to the cytochrome C apoprotein to produce the mature functional cytochrome.

100 Clinical Results associated with HCCS

100 Translational Medicine associated with HCCS

0 Patents (Medical) associated with HCCS

547

Literatures (Medical) associated with HCCS

11 Apr 2025·ACS Infectious Diseases

Biogenesis of Cytochromes c and c₁ in the Electron Transport Chain of Malaria Parasites

Article

Author: Marvin, Rebecca G. ; Blackwell, Amanda Mixon ; Sigala, Paul A. ; García-Guerrero, Aldo E.

Plasmodium malaria parasites retain an essential mitochondrional electron transport chain (ETC) that is critical for growth within humans and mosquitoes and is a key antimalarial drug target. ETC function requires cytochromes c and c₁, which are unusual among heme proteins due to their covalent binding to heme via conserved CXXCH sequence motifs. Heme attachment to these proteins in most eukaryotes requires the mitochondrial enzyme holocytochrome c synthase (HCCS) that binds heme and the apo cytochrome to facilitate the biogenesis of the mature cytochrome c or c₁. Although humans encode a single bifunctional HCCS that attaches heme to both proteins, Plasmodium parasites are like yeast and encode two separate HCCS homologues thought to be specific for heme attachment to cyt c (HCCS) or cyt c₁ (HCC₁S). To test the function and specificity of Plasmodium falciparum HCCS and HCC₁S, we used CRISPR/Cas9 to tag both genes for conditional expression. HCC₁S knockdown selectively impaired cyt c₁ biogenesis and caused lethal ETC dysfunction that was not reversed by the overexpression of HCCS. Knockdown of HCCS caused a more modest growth defect but strongly sensitized parasites to mitochondrial depolarization by proguanil, revealing key defects in ETC function. These results and prior heterologous studies in Escherichia coli of cyt c hemylation by P. falciparum HCCS and HCC₁S strongly suggest that both homologues are essential for mitochondrial ETC function and have distinct specificities for the biogenesis of cyt c and c₁, respectively, in parasites. This study lays a foundation to develop novel strategies to selectively block ETC function in malaria parasites.

01 Dec 2024·Environmental Research

Spatiotemporal distribution of the planktonic microbiome and antibiotic resistance genes in a typical urban river contaminated by macrolide antibiotics

Article

Author: Guo, Jiahua ; Yang, Chuanmao ; Zhang, Baihuan ; Yao, Xiunan ; Mo, Jiezhang ; Rehman, Fozia ; Yan, Shiwei

The widespread application of macrolide antibiotics has caused antibiotic resistance pollution, threatening the river ecological health. In this study, five macrolide antibiotics (azithromycin, clarithromycin, roxithromycin, erythromycin, and anhydro erythromycin A) were monitored in the Zao River across three hydrological periods (April, July, and December). Simultaneously, the changes in antibiotic resistance genes (ARGs), mobile genetic elements (MGEs), and planktonic bacterial communities were determined using metagenomic sequencing. A clear pollution gradient was observed for azithromycin and roxithromycin, with the concentrations in the dry season surpassing those in other seasons. The highest concentration was observed for azithromycin (1.36 μg/L). The abundance of MLS resistance genes increased along the Zao River during the dry season, whereas the opposite trend was obtained during the wet season. A significant correlation between the levels of MLS resistance genes and macrolide antibiotics was identified during the dry season. Notably, compared with the reference site, the abundance of transposase in the effluent from wastewater treatment plants (WWTPs) was significantly elevated in both dry and wet seasons, whereas the abundance of insertion sequences (IS) and plasmids declined during the dry season. The exposure to wastewater containing macrolide antibiotics altered the diversity of planktonic bacterial communities. The bacterial host for ARGs appeared to be Pseudomonas, primarily associated with multidrug subtypes. Moreover, the ARG subtypes were highly correlated with MGEs (transposase and istA). The partial least-squares path model (PLS-PM) demonstrated a positive correlation between the abundance of MGEs and ARGs, indicating the significance of horizontal gene transfer (HGT) in the dissemination of ARGs within the Zao River. Environmental variables, such as TN and NO₃^--N, were significantly correlated with the abundance of MGEs, ARGs, and bacteria. Collectively, our findings could provide insights into the shift patterns of the microbiome and ARGs across the contamination gradient of AZI and ROX in the river.

01 Nov 2024·Chemosphere

Anxiety caused by chronic exposure to methylisothiazolinone in zebrafish: Behavioral analysis, brain histology and gene responses

Article

Author: Li, Rui ; Xia, Weili ; Hu, Junxia ; Zhang, Yuanqing ; Hu, Xinyuan ; Fan, Xuesong ; Song, Tianjia ; Yu, Tiangui ; Qu, Jiangbo

Methylisothiazolinones (MIT) are a class of preservatives and biocides extensively utilized in everyday products, industrial processes, and medical and healthcare applications. However, reports have indicated that MIT may cause skin irritation and neurotoxicity. Given its pervasive use, the neurotoxic potential of MIT has garnered increasing attention. Recent in vitro cellular experiments have demonstrated that MIT inhibits synaptic growth, although the neurotoxic effects and underlying mechanisms at the organismal level remain largely unexplored. In this study, it was found for the first time that long-term exposure to MIT resulted in anxiety, brain tissue inflammation, and a reduction in the number of Nissl bodies in the brain. Additionally, transcriptomic analysis indicated that exposure to 300 μg/L MIT induced a greater number of differentially expressed genes compared to 30 μg/L MIT, relative to the control group. Enrichment analysis, trend analysis, and GSEA analysis collectively identified the involvement of Steroid hormone metabolism, oxidative metabolism, and the Hedgehog pathway in MIT-induced neurotoxicity. Furthermore, a subsequent reduction in green fluorescence was observed in the MLS-EGFP zebrafish strain larvae of the HD group, suggesting that high dosage of MIT exerts an inhibitory effect on mitochondrial activity. This study confirmed the neurotoxic effects of MIT and investigated the potential genetic networks behind anxiety behavior. These findings contributed to the identification of key brain genes involved in the detection and monitoring of MIT, offering new insights into the neuroendocrine toxicity of other imidazolidinone compounds.

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HCCS

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