Evidence map›Paper›PMID 42302176›Full record

ArticleThe Journal of clinical investigation2026

Elevated mitochondrial protein import in acute myeloid leukemia increases reliance on mitochondrial protease LONP1.

Matthew Tcheng, Veronique Voisin, Geethu Emily Thomas, Anastasija A Piric, Marcela Gronda, Rose Hurren, Dakai Ling, Yongran Yan, Lan Xin Zhang, Yue Feng and 20 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of clinical investigation, 2026. 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

30 authors.

Matthew TchengPrincess Margaret Cancer Centre.
Veronique VoisinPrincess Margaret Cancer Centre.
Geethu Emily ThomasPrincess Margaret Cancer Centre.
Anastasija A PiricPrincess Margaret Cancer Centre.
Marcela GrondaPrincess Margaret Cancer Centre.
Rose HurrenPrincess Margaret Cancer Centre.
Dakai LingPrincess Margaret Cancer Centre.
Yongran YanPrincess Margaret Cancer Centre.
Lan Xin ZhangPrincess Margaret Cancer Centre.
Yue FengPrincess Margaret Cancer Centre.
Ali CheginiPrincess Margaret Cancer Centre.
Nathan DuongPrincess Margaret Cancer Centre.
Ross S ManciniKrembil Brain Institute, University Health Network, Toronto, Ontario, Canada.
Stefan Quinn W CurrieDepartment of Molecular and Cell Biology, University of Guelph, Guelph, Ontario, Canada.
Zaynab MamaiPrincess Margaret Cancer Centre.
Brady StockPrincess Margaret Cancer Centre.
Shahbaz KhanPrincess Margaret Cancer Centre.
Yulia JitkovaPrincess Margaret Cancer Centre.
Chaitra SarathyPrincess Margaret Cancer Centre.
Edward AyoubSection of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Po Yee MakSection of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Andrea ArrudaPrincess Margaret Cancer Centre.
Thomas KislingerPrincess Margaret Cancer Centre.
Mark A ReedKrembil Brain Institute, University Health Network, Toronto, Ontario, Canada.
Bing Z CarterSection of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Michael AndreeffSection of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Steven M KornblauSection of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Mark D MindenPrincess Margaret Cancer Centre.
Siavash VahidiDepartment of Molecular and Cell Biology, University of Guelph, Guelph, Ontario, Canada.
Aaron D SchimmerPrincess Margaret Cancer Centre.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Most mitochondrial proteins are nucleus-encoded, translated in the cytosol, and imported into the mitochondria. Through gene expression analysis and functional assays, we demonstrated that mitochondrial protein import was increased in acute myeloid leukemia (AML) cells compared with normal hematopoietic cells. Increased mitochondrial protein import was positively correlated with an increase in the mitochondrial unfolded protein response (UPRmt), a stress-activated pathway of mitochondrial proteases and chaperones that maintains protein solubility and prevents the formation of toxic aggregates. The UPRmt protease LONP1 (Lon peptidase 1) was upregulated in AML and positively correlated with increased mitochondrial protein import and UPRmt. Genetic or chemical inhibition of the LONP1 ATPase domain induced mitochondrial protein aggregation and selectively killed AML cells with high LONP1 expression, while sparing AML cells with low LONP1 expression and normal hematopoietic cells in vitro and in vivo. Thus, we uncovered a critical role of the UPRmt protease LONP1 in buffering stress from mitochondrial protein import in AML.

Indexed as

ATP-Dependent ProteasesLeukemia, Myeloid, AcuteMitochondriaMitochondrial ProteinsNeoplasm ProteinsUnfolded Protein ResponseAnimalsCell Line, TumorHumansMiceProtein TransportATP-Dependent ProteasesLONP1 protein, humanMitochondrial ProteinsNeoplasm ProteinsCancerCell biologyMetabolismOncology

Identifiers

PMID42302176
PMCPMC13430017

What OpenQuestion holds

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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.