Evidence map›Paper›PMID 39726060›Full record

ArticleTranslational neurodegeneration2024

SARS-CoV-2 membrane protein induces neurodegeneration via affecting Golgi-mitochondria interaction.

Fang Wang, Hailong Han, Caifang Wang, Jingfei Wang, Yanni Peng, Ye Chen, Yaohui He, Zhouyang Deng, Fang Li, Yikang Rong and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Translational neurodegeneration, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Fang Wang *Department of Neurosciences, Hengyang Medical School, University of South China, Hengyang, 421009, China.
Hailong Han *Department of Neurosciences, Hengyang Medical School, University of South China, Hengyang, 421009, China.
Caifang WangInstitute of Molecular Precision Medicine and Hunan Provincial Key Laboratory of Molecular Precision Medicine, Xiangya Hospital, Central South University, Changsha, 410078, China.
Jingfei WangState Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150001, China.
Yanni PengInstitute of Molecular Precision Medicine and Hunan Provincial Key Laboratory of Molecular Precision Medicine, Xiangya Hospital, Central South University, Changsha, 410078, China.
Ye ChenInstitute of Molecular Precision Medicine and Hunan Provincial Key Laboratory of Molecular Precision Medicine, Xiangya Hospital, Central South University, Changsha, 410078, China.
Yaohui HeFujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen, 361000, China.
Zhouyang DengHunan Provincial Key Laboratory of Medical Genetics, College of Biological Sciences, Central South University, Changsha, 410078, China.
Fang LiHunan Provincial Key Laboratory of Medical Genetics, College of Biological Sciences, Central South University, Changsha, 410078, China.
Yikang RongDepartment of Neurosciences, Hengyang Medical School, University of South China, Hengyang, 421009, China.
Danling WangDepartment of Neurosciences, Hengyang Medical School, University of South China, Hengyang, 421009, China.
Wen LiuFujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen, 361000, China.
Hualan ChenState Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150001, China.
Zhuohua ZhangDepartment of Neurosciences, Hengyang Medical School, University of South China, Hengyang, 421009, China. zhangzhuohua@sklmg.edu.cn.ORCID 0000-0002-1394-0697

Funding

a Key Laboratory Grant from Hunan Provincial Science and Technology Department 2016TP1006Science and Technology Innovation Program of Hunan Province 2021SK1014Science and Technology Major Project of Hunan Provincial Science and Technology Department 2018SK1030The China Postdoctoral Science Foundation 271004the Discipline Innovative Engineering Plan (111 Program) of China B13036the National Natural Science Foundation of China 31330031the National Natural Science Foundation of China 31872778the National Natural Science Foundation of China 81429002the National Natural Science Foundation of China 82201412
6 · The paper itself

Abstract

backgroundNeurological complications are a significant concern of Coronavirus Disease 2019 (COVID-19). However, the pathogenic mechanism of neurological symptoms associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is poorly understood.

methodsWe used Drosophila as a model to systematically analyze SARS-CoV-2 genes encoding structural and accessory proteins and identified the membrane protein (M) that disrupted mitochondrial functions in vivo. The M protein was stereotaxically injected to further assess its effects in the brains of wild-type (WT) and 5 × FAD mice. Omics technologies, including RNA sequencing and interactome analysis, were performed to explore the mechanisms of the effects of M protein both in vitro and in vivo.

resultsSystematic analysis of SARS-CoV-2 structural and accessory proteins in Drosophila identified that the M protein induces mitochondrial fragmentation and dysfunction, leading to reduced ATP production, ROS overproduction, and eventually cell death in the indirect flight muscles. In WT mice, M caused hippocampal atrophy, neural apoptosis, glial activation, and mitochondrial damage. These changes were further aggravated in 5 × FAD mice. M was localized to the Golgi apparatus and genetically interacted with four wheel drive (FWD, a Drosophila homolog of mammalian PI4KIIIβ) to regulate Golgi functions in flies. Fwd RNAi, but not PI4KIIIα RNAi, reversed the M-induced Golgi abnormality, mitochondrial fragmentation, and ATP reduction. Inhibition of PI4KIIIβ activity suppressed the M-induced neuronal cell death. Therefore, M induced mitochondrial fragmentation and apoptosis likely through disruption of Golgi-derived PI(4)P-containing vesicles.

conclusionsM disturbs the distribution and function of Golgi, leading to mitochondrial abnormality and eventually neurodegeneration via a PI4KIIIβ-mediated mechanism. This study reveals a potential mechanism for COVID-19 neurological symptoms and opens a new avenue for development of therapeutic strategies targeting SARS-CoV-2 M or mitochondria.

Indexed as

COVID-19Golgi ApparatusMitochondriaSARS-CoV-2AnimalsCoronavirus M ProteinsDisease Models, AnimalDrosophilaDrosophila melanogasterDrosophila ProteinsHumansMiceNeurodegenerative DiseasesCoronavirus M ProteinsDrosophila ProteinsAlzheimer’s diseaseBrainCOVID-19MitochondriaPI4KIIIβ

Identifiers

PMID39726060
PMCPMC11674522

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.