Evidence map›Paper›PMID 40674424›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2025

mtKO: A dedicated guide RNA library for mitochondria research.

Karambir Kaur, Javeria Zaheer, Fengchao Lang, Diego Luis Ribeiro, Meili Zhang, Hua Song, Wei Zhang, Raj Chari, Hussam Alkaissi, Chunzhang Yang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

10 authors.

Karambir Kaur *Neuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892.
Javeria Zaheer *Neuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892.
Fengchao Lang *Neuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892.
Diego Luis RibeiroNeuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892.
Meili ZhangNeuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892.
Hua SongNeuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892.
Wei ZhangNeuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892.
Raj ChariLaboratory Animal Sciences Program, Genome Modification Core, Frederick National Laboratory for Cancer Research, Frederick, MD 21702.
Hussam AlkaissiNational Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH, Bethesda, MD 20892.
Chunzhang YangNeuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892.ORCID 0000-0001-6433-0867

Funding

NCI NIH HHS HHSN261201500003CNCI NIH HHS HHSN261201500003I
6 · The paper itself

Abstract

Mitochondria are multifunctional organelles central to both physiological and pathological processes. In malignant cancer cells, mitochondrial reprogramming establishes the metabolic foundation to meet cellular demands, which is particularly important in tumor cells with existing metabolic perturbations. To identify key mitochondrial pathways supporting cancer development, we developed mitochondria Knockout (mtKO), a robust and unbiased CRISPR screening platform to pinpoint critical mitochondria-associated pathways. The mtKO screen revealed that the mitochondrial antioxidant enzyme SOD2 is essential for cells harboring IDH1 mutations. Mechanistically, SOD2 activity determines the disease manifestation of IDH1-mutated cancers, through maintaining redox homeostasis and mitochondrial fitness. This study introduces a powerful functional genomic tool to identify mitochondrial-centered pathways and reveals the selective mitochondrial vulnerability in Krebs cycle-deficient cancers for future therapeutic intervention.

Indexed as

MitochondriaRNA, Guide, CRISPR-Cas SystemsSuperoxide DismutaseAnimalsCell Line, TumorCRISPR-Cas SystemsGene Knockout TechniquesGene LibraryHumansIsocitrate DehydrogenaseMutationNeoplasmsSuperoxide Dismutase 2Isocitrate DehydrogenaseRNA, Guide, CRISPR-Cas SystemsSuperoxide DismutaseSuperoxide Dismutase 2CRISPR screenIDH1metabolismmitochondriaSOD2

Identifiers

PMID40674424
PMCPMC12304920

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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 OpenQuestion graph.