ArticleiScience2023
SARS-CoV-2 ORF3c impairs mitochondrial respiratory metabolism, oxidative stress, and autophagic flux.
Article in iScience, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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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.
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.
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Who cites it
18 citing papers in PubMed, 26 citations in OpenAlex.
- Computational proteomics to enhance personalized treatment of COVID-19 and Long COVID.Clinical proteomics · 2026Review
- SARS-CoV-2 altered mitochondrial DNA methylation in Indian COVID-19 patients.Scientific reports · 2026Article
- Mechanisms of Mitochondrial Impairment by SARS-CoV-2 Proteins: A Nexus of Pathogenesis with Significant Biochemical and Clinical Implications.International journal of molecular sciences · 2025Review
- Mitochondrial Reactive Oxygen Species: A Unifying Mechanism in Long COVID and Spike Protein-Associated Injury: A Narrative Review.Biomolecules · 2025Review
- Different Expression of Nuclear Respiratory Factor 1 (NRF-1) Gene in COVID-19: An Insight into Disease Severity.Current microbiology · 2025Article
- Mitochondria and the Repurposing of Diabetes Drugs for Off-Label Health Benefits.International journal of molecular sciences · 2025Review
- Hidden players of COVID-19: the evolving roles of SARS-CoV-2 accessory proteins.Frontiers in immunology · 2025Review
- Article
- Review
- Post-Acute Sequelae and Mitochondrial Aberration in SARS-CoV-2 Infection.International journal of molecular sciences · 2024Review
- SARS-CoV-2, periodontal pathogens, and host factors: The trinity of oral post-acute sequelae of COVID-19.Reviews in medical virology · 2024Review
- SARS-CoV-2 and innate immunity: the good, the bad, and the "goldilocks".Cellular & molecular immunology · 2024Review
- Article
- ORF3c is expressed in SARS-CoV-2-infected cells and inhibits innate sensing by targeting MAVS.EMBO reports · 2023Article
- Review
- The Role of Immune Dysfunction in Parkinson's Disease Development.International journal of molecular sciences · 2023Review
- Article
- Host mitochondria: more than an organelle in SARS-CoV-2 infection.Frontiers in cellular and infection microbiology · 2023Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Coronaviruses encode a variable number of accessory proteins that are involved in host-virus interaction, suppression of immune responses, or immune evasion. SARS-CoV-2 encodes at least twelve accessory proteins, whose roles during infection have been studied. Nevertheless, the role of the ORF3c accessory protein, an alternative open reading frame of ORF3a, has remained elusive. Herein, we show that the ORF3c protein has a mitochondrial localization and alters mitochondrial metabolism, inducing a shift from glucose to fatty acids oxidation and enhanced oxidative phosphorylation. These effects result in increased ROS production and block of the autophagic flux. In particular, ORF3c affects lysosomal acidification, blocking the normal autophagic degradation process and leading to autolysosome accumulation. We also observed different effect on autophagy for SARS-CoV-2 and batCoV RaTG13 ORF3c proteins; the 36R and 40K sites are necessary and sufficient to determine these effects.
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What OpenQuestion holds
Registered trials
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 OpenQuestion graph.