Evidence map›Paper›PMID 38007588›Full record

ArticleCommunications medicine2023

O-GlcNAcylation is essential for therapeutic mitochondrial transplantation.

Ji Hyun Park, Masayoshi Tanaka, Takafumi Nakano, Ester Licastro, Yoshihiko Nakamura, Wenlu Li, Elga Esposito, Emiri T Mandeville, Sherry Hsiang-Yi Chou, MingMing Ning and 2 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Communications medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.6field-weighted citation impact, top 10% of its field
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

13 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. Review
  3. Therapeutic Potential of Mitochondrial Transplantation with Focus on DBD.International journal of molecular sciences · 2026
    Review
  4. Review
  5. Article
  6. Article
  7. Review
  8. Review
  9. Article
  10. Frontiers in immunology · 2025
    Review
  11. Review
  12. Review
  13. Review
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

12 authors at 2 institutions in 1 country.

Ji Hyun ParkNeuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
Masayoshi TanakaNeuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
Takafumi NakanoNeuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
Ester LicastroNeuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.ORCID http://orcid.org/0000-0001-6917-4605
Yoshihiko NakamuraNeuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
Wenlu LiNeuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.ORCID http://orcid.org/0000-0001-6507-392X
Elga EspositoNeuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
Emiri T MandevilleNeuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.ORCID http://orcid.org/0000-0002-7680-0923
Sherry Hsiang-Yi ChouNeuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
MingMing NingNeuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
Eng H LoNeuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA. Lo@helix.mgh.harvard.edu.ORCID http://orcid.org/0000-0002-9327-2915
Kazuhide HayakawaNeuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA. khayakawa1@mgh.harvard.edu.ORCID http://orcid.org/0000-0002-1229-2413
Harvard University · USBrigham and Women's Hospital · US

Funding

Proteomic Profiling of Patent Foramen Ovale Related Neurovascular InjuryR01NS067139 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI NING, MINGMING · 2010 to 2023
$3.7M
Extracellular Mitochondria Transfer in Gray and White Matter for Ameliorating Sensorimotor and Cognitive Deficits After StrokeR01NS126280 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI Kazuhide Hayakawa · 2022 to 2026
$2.5M
NINDS NIH HHS R01 NS067139NINDS NIH HHS R01 NS126280
6 · The paper itself

Abstract

backgroundTransplantation of mitochondria is increasingly explored as a novel therapy in central nervous system (CNS) injury and disease. However, there are limitations in safety and efficacy because mitochondria are vulnerable in extracellular environments and damaged mitochondria can induce unfavorable danger signals.

methodsMitochondrial O-GlcNAc-modification was amplified by recombinant O-GlcNAc transferase (OGT) and UDP-GlcNAc. O-GlcNAcylated mitochondrial proteins were identified by mass spectrometry and the antiglycation ability of O-GlcNAcylated DJ1 was determined by loss-of-function via mutagenesis. Therapeutic efficacy of O-GlcNAcylated mitochondria was assessed in a mouse model of transient focal cerebral ischemia-reperfusion. To explore translational potential, we evaluated O-GlcNAcylated DJ1 in CSF collected from patients with subarachnoid hemorrhagic stroke (SAH).

resultsWe show that isolated mitochondria are susceptible to advanced glycation end product (AGE) modification, and these glycated mitochondria induce the receptor for advanced glycation end product (RAGE)-mediated autophagy and oxidative stress when transferred into neurons. However, modifying mitochondria with O-GlcNAcylation counteracts glycation, diminishes RAGE-mediated effects, and improves viability of mitochondria recipient neurons. In a mouse model of stroke, treatment with extracellular mitochondria modified by O-GlcNAcylation reduces neuronal injury and improves neurologic deficits. In cerebrospinal fluid (CSF) samples from SAH patients, levels of O-GlcNAcylation in extracellular mitochondria correlate with better clinical outcomes.

conclusionsThese findings suggest that AGE-modification in extracellular mitochondria may induce danger signals, but O-GlcNAcylation can prevent glycation and improve the therapeutic efficacy of transplanted mitochondria in the CNS.

Identifiers

PMID38007588
PMCPMC10676354
OpenAlexW4388997774

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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.