Toxoplasma gondii autophagy-related protein ATG7 maintains apicoplast inheritance by stabilizing and lipidating ATG8

doi:10.1016/j.bbadis.2023.166891

科研成果详情

题名	Toxoplasma gondii autophagy-related protein ATG7 maintains apicoplast inheritance by stabilizing and lipidating ATG8
作者	Wu, Mimi1,2; Ying, Jiaqi3; Lin, Xuejing2; Xu, Chao1; Zheng, Xiaozi4; Zheng, Yi5; Fang, Zhouxi6; Yan, Baolong2; Zhang, Nu1; Mou, Yani2; Tan, Feng1,2
发表日期	2024-01
发表期刊	Biochimica et biophysica acta. Molecular basis of disease 影响因子和分区
语种	英语
原始文献类型	Journal Article
关键词	ATG7 ATG8 Apicoplast Autophagy Toxoplasma gondii Ubiquitination
其他关键词	PROTEASOMAL DEGRADATION ; E2 RECRUITMENT ; E1 ; MECHANISM ; ENZYME ; LC3 ; UBIQUITINATION ; RECOGNITION ; ACTIVATION ; ATG7-ATG3
摘要	ATG8/LC3-mediated autophagosome formation is a key rate-limiting step in the process of autophagy. The parasitic protist Toxoplasma gondii possesses a single ATG8 homolog (TgATG8), which can localize to either cytosolic autophagosome involved in delivery of autophagic material in bradyzoites, or the outermost membrane of apicoplast, a nonphotosynthetic plastid-like organelle, responsible for maintaining homeostasis in tachyzoites. However, mechanisms that regulate TgATG8 remain insufficiently understood. Here, a TgATG7 conditional knockdown line that we have generated is severely impaired in parasite's growth and exhibits significant defects in the organelle level, strikingly with a fragmentation of the mitochondrial network and a loss of the apicoplast. Specific TgATG7C1133S point mutant complemented line showed that these defects were associated with its E1-type enzyme activity. Both depletion of TgATG7 and mutation of its catalytic cysteine 1133 hindered TgATG8 lipidation and apicoplast localization. Unexpectedly, we also found that depletion of TgATG7 reduced the unlipidated TgATG8 protein level. Subsequently, we determined that TgATG7 was able to interact with TgATG8 directly via its C-terminal domain and multi-monoubiquitination stimulated proteasome-dependent degradation of TgATG8, while TgATG7 could inhibit the degradation through stabilization of TgATG8. Additionally, we identified a putative TgATG8 interacting fragment of TgATG7, 1281-1290aa. Depletion of the fragment impaired the parasite growth and apicoplast inheritance. To our knowledge, our study is the first to elucidate the role of TgATG7 and the ubiquitin-proteasome system in synergistically regulating the non-lipidated pool of TgATG8, suggesting a potential homeostatic mechanism responsible for balancing autophagic activity in T. gondii
资助项目	National Natural Science Foundation of China [81971962, LZ22H190001]; Key Project of Natural Science Foundation of Zhejiang Province; [82172303]
出版者	ELSEVIER
ISSN	0925-4439
EISSN	1879-260X
卷号	1870 期号:1
DOI	10.1016/j.bbadis.2023.166891
页数	16
WOS类目	Biochemistry & Molecular Biology ; Biophysics ; Cell Biology
WOS研究方向	Biochemistry & Molecular Biology ; Biophysics ; Cell Biology
WOS记录号	WOS:001082070800001
收录类别	PUBMED ; SCIE ; SCOPUS
URL	查看原文
PubMed ID	37739091
SCOPUSEID	2-s2.0-85171748617
通讯作者地址	[Zhang, Nu]The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University,Wenzhou Medical University,Zhejiang,Wenzhou,China ; [Tan, Feng]The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University,Wenzhou Medical University,Zhejiang,Wenzhou,China
Scopus学科分类	Molecular Medicine;Molecular Biology
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/182986
专题	第二临床医学院、附属第二医院、育英儿童医院基础医学院（机能实验教学中心）检验医学院（生命科学学院、生物学实验教学中心）附属第二医院检验医学院（生命科学学院、生物学实验教学中心）_模式生物技术与应用重点实验室基础医学院（机能实验教学中心）_基础医学实验教学中心_形态实验教学中心
通讯作者	Zhang, Nu; Tan, Feng
作者单位	1.The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University,Wenzhou Medical University,Zhejiang,Wenzhou,China; 2.Department of Parasitology,School of Basic Medical Sciences,Wenzhou Medical University,Zhejiang,Wenzhou,China; 3.School of the Second Clinical Medical Sciences,Wenzhou Medical University,Zhejiang,Wenzhou,China; 4.Teaching Center of Morphological Experiment,School of Basic Medical Sciences,Wenzhou Medical University,Zhejiang,Wenzhou,China; 5.Laser Confocal Microscope Lab,School of Laboratory Medicine and Life Sciences,Wenzhou Medical University,Zhejiang,Wenzhou,China; 6.Zhejiang Provincial Key Laboratory for Technology and Application of Model Organisms,Key Laboratory of Laboratory Medicine,Ministry of Education,School of Laboratory Medicine and Life Sciences,Wenzhou Medical University,Zhejiang,Wenzhou,China
第一作者单位	第二临床医学院，附属第二医院、育英儿童医院; 附属第二医院; 基础医学院（机能实验教学中心）
通讯作者单位	第二临床医学院，附属第二医院、育英儿童医院; 附属第二医院
第一作者的第一单位	第二临床医学院，附属第二医院、育英儿童医院
推荐引用方式 GB/T 7714	Wu, Mimi,Ying, Jiaqi,Lin, Xuejing,et al. Toxoplasma gondii autophagy-related protein ATG7 maintains apicoplast inheritance by stabilizing and lipidating ATG8[J]. Biochimica et biophysica acta. Molecular basis of disease,2024,1870(1).
APA	Wu, Mimi., Ying, Jiaqi., Lin, Xuejing., Xu, Chao., Zheng, Xiaozi., ... & Tan, Feng. (2024). Toxoplasma gondii autophagy-related protein ATG7 maintains apicoplast inheritance by stabilizing and lipidating ATG8. Biochimica et biophysica acta. Molecular basis of disease, 1870(1).
MLA	Wu, Mimi,et al."Toxoplasma gondii autophagy-related protein ATG7 maintains apicoplast inheritance by stabilizing and lipidating ATG8".Biochimica et biophysica acta. Molecular basis of disease 1870.1(2024).