Evidence map›Paper›PMID 42421121›Full record

ArticleTranslational neurodegeneration2026

Plant-derived mitochondria mitigate aging-related neurodegeneration by reprogramming microglial mitochondrial energy metabolism.

Yun Teng, Chao Luo, Qingbo Xu, Jingyao Mu, Lucy Teng, Hongjia Qian, Yinan Huang, Minmin Liu, Lifeng Zhang, Juw Won Park and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Translational neurodegeneration, 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

15 authors.

Yun Teng *Brown Cancer Center, Department of Medicine, University of Louisville School of Medicine, CTRB Room 309, 505 S. Hancock Street, Louisville, KY, 40202, USA. yun.teng@louisville.edu.
Chao Luo *Brown Cancer Center, Department of Medicine, University of Louisville School of Medicine, CTRB Room 309, 505 S. Hancock Street, Louisville, KY, 40202, USA.
Qingbo Xu *Department of Microbiology and Immunology, University of Louisville, Louisville, KY, USA.
Jingyao MuBrown Cancer Center, Department of Medicine, University of Louisville School of Medicine, CTRB Room 309, 505 S. Hancock Street, Louisville, KY, 40202, USA.
Lucy TengDepartment of Microbiology and Immunology, University of Louisville, Louisville, KY, USA.
Hongjia QianBrown Cancer Center, Department of Medicine, University of Louisville School of Medicine, CTRB Room 309, 505 S. Hancock Street, Louisville, KY, 40202, USA.
Yinan HuangBrown Cancer Center, Department of Medicine, University of Louisville School of Medicine, CTRB Room 309, 505 S. Hancock Street, Louisville, KY, 40202, USA.
Minmin LiuBrown Cancer Center, Department of Medicine, University of Louisville School of Medicine, CTRB Room 309, 505 S. Hancock Street, Louisville, KY, 40202, USA.
Lifeng ZhangBrown Cancer Center, Department of Medicine, University of Louisville School of Medicine, CTRB Room 309, 505 S. Hancock Street, Louisville, KY, 40202, USA.
Juw Won ParkBrown Cancer Center, Department of Medicine, University of Louisville School of Medicine, CTRB Room 309, 505 S. Hancock Street, Louisville, KY, 40202, USA.
Jae Yeon HwangBrown Cancer Center, Department of Medicine, University of Louisville School of Medicine, CTRB Room 309, 505 S. Hancock Street, Louisville, KY, 40202, USA.
Maiying KongBrown Cancer Center, Department of Medicine, University of Louisville School of Medicine, CTRB Room 309, 505 S. Hancock Street, Louisville, KY, 40202, USA.
Jun YanBrown Cancer Center, Department of Medicine, University of Louisville School of Medicine, CTRB Room 309, 505 S. Hancock Street, Louisville, KY, 40202, USA.
Michael L MerchantKidney Disease Program and Clinical Proteomics Center, University of Louisville, Louisville, KY, USA.
Huang-Ge ZhangDepartment of Microbiology and Immunology, University of Louisville, Louisville, KY, USA. h0zhan17@louisville.edu.

Funding

NIH HHS R01AT008617-06ARobley Rex VA Medical Center Merit IK6BX004199
6 · The paper itself

Abstract

backgroundIntercellular mitochondrial transfer is pivotal in both healthy and pathological states. Supplementing healthy mitochondria is emerging as a promising therapeutic approach for various diseases. Non-immunogenic edible plants, which contain mitochondria, offer a novel avenue for such therapies.

methodsMitochondria were isolated from several commonly consumed edible plants (P-Mit) using differential centrifugation followed by sucrose gradient ultracentrifugation. The distribution of P-Mit, particularly in the brain, was examined with a mitochondrial membrane-potential dye and an imaging system. As a proof of concept, the molecular interactions underlying turmeric-derived mitochondria (T-Mit) uptake by microglia were elucidated through affinity precipitation coupled with mass spectrometry. By labeling with gold-nanoparticles in a distinct triangular or spherical shape followed by electron microscopy and energy dispersive spectroscopy analysis, we demonstrated the physical fusion of T-Mit and animal mitochondria in microglia. Mitochondrial functions such as superoxide levels, ATP-linked mitochondrial respiration, glycolysis and electron transport chain activity were assessed to determine the impact of T-Mit on aging-related microglial dysfunction. Next-generation small RNA sequencing revealed the underlying mechanism by which T-Mit-derived small RNAs modulate the expression of NADH dehydrogenase (ND) genes in microglia.

resultsOrally administered T-Mit travelled from the gut to the brain in aged male mice, where they fused with microglial mitochondria (M-Mit), reprogramming M-Mit energy metabolism and reversing aging-related cognitive dysfunction. Specifically, T-Mit was taken up by microglia via the phagocytic receptor TREM2. Subsequently, T-Mit fused with M-Mit in a mitofusin 1-dependent manner. The T-Mit microRNAs Tae-miR319 and Osa-miR166a-3p then integrated into M-Mit, inhibiting the expression of complex I subunits ND4 and ND5. This inhibition alleviated reverse electron transport (RET) at complex I, reducing reactive oxygen species (ROS) production and facilitating ATP production, ultimately rescuing aging-related cognitive decline. Data from elderly human subjects also showed overactivation of the RET process and overproduction of ROS, accompanied by low ATP levels in microglia.

conclusionsOur findings fundamentally alter our understanding of the regulation of mammalian mitochondrial biology by P-Mit and may lead to P-Mit-based transfer therapy for preventing or treating human mitochondrial disorder-related diseases.

Indexed as

AgingEnergy MetabolismMicrogliaMitochondriaNeurodegenerative DiseasesAnimalsMaleMiceMice, Inbred C57BLAging-related neurodegenerationCardiolipinCross-kingdom mitochondrial fusionMicroglia mitochondrial metabolismMitochondria transfer therapyNADH dehydrogenase (Complex I)Plant mitochondriaPlant mitochondrial microRNAsReactive oxygen species (ROS)Reverse electron transport (RET)

Identifiers

PMID42421121
PMCPMC13343874

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.