Evidence map›Paper›PMID 32180546›Full record

ArticleeLife2020

Chemoptogenetic ablation of neuronal mitochondria in vivo with spatiotemporal precision and controllable severity.

Wenting Xie, Binxuan Jiao, Qing Bai, Vladimir A Ilin, Ming Sun, Charles E Burton, Dmytro Kolodieznyi, Michael J Calderon, Donna B Stolz, Patricia L Opresko and 5 more

Open access · goldAbstract read
In one paragraph

Article in eLife, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

15 citing papers in PubMed, 25 citations in OpenAlex.

  1. Article
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  9. Review
  10. Targeted Formation of 8-Oxoguanine in Telomeres.Methods in molecular biology (Clifton, N.J.) · 2022
    Article
  11. Article
  12. Article
  13. Mechanism of Pacemaker Activity in Zebrafish DC2/4 Dopaminergic Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021
    Article
  14. Article
  15. Article
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 at 4 institutions in 2 countries.

Wenting Xie *Department of Neurology, University of Pittsburgh, Pittsburgh, United States.
Binxuan Jiao *Department of Neurology, University of Pittsburgh, Pittsburgh, United States.
Qing Bai *Department of Neurology, University of Pittsburgh, Pittsburgh, United States.
Vladimir A Ilin *Department of Neurology, University of Pittsburgh, Pittsburgh, United States.
Ming SunCenter for Biologic Imaging, University of Pittsburgh, Pittsburgh, United States.
Charles E BurtonWinchester Thurston School, Pittsburgh, United States.
Dmytro KolodieznyiDepartments of Biological Sciences and Chemistry, Carnegie Mellon University, Pittsburgh, United States.ORCID 0000-0001-5272-6856
Michael J CalderonCenter for Biologic Imaging, University of Pittsburgh, Pittsburgh, United States.
Donna B StolzCenter for Biologic Imaging, University of Pittsburgh, Pittsburgh, United States.
Patricia L OpreskoDepartment of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, United States.
Claudette M St CroixCenter for Biologic Imaging, University of Pittsburgh, Pittsburgh, United States.
Simon WatkinsCenter for Biologic Imaging, University of Pittsburgh, Pittsburgh, United States.ORCID 0000-0003-4092-1552
Bennett Van HoutenGenome Stability Program, UPMC Hillman Cancer Center, Pittsburgh, United States.
Marcel P BruchezDepartments of Biological Sciences and Chemistry, Carnegie Mellon University, Pittsburgh, United States.ORCID 0000-0002-7370-4848
Edward A BurtonDepartment of Neurology, University of Pittsburgh, Pittsburgh, United States.ORCID 0000-0002-8072-4636
University of Pittsburgh · USCarnegie Mellon University · USImaging Center · USWinchester Hospital · US

Funding

Targeted fluorescent indicators for endothelial physiology: Ca(II), ROS, NOR01EB017268 · NIBIB · CARNEGIE-MELLON UNIVERSITY · PI BRUCHEZ, MARCEL P, ST CROIX, CLAUDETTE MARIE · 2013 to 2016
$2.5M
Pathogenic mechanisms of gene-environment interactions in Parkinson's diseaseR01ES022644 · NIEHS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BURTON, EDWARD ALAN · 2014 to 2018
$1.7M
ROS driven mitochondrial-telomere dysfunction during environmental stressR33ES025606 · NIEHS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI OPRESKO, PATRICIA L, VAN HOUTEN, BENNETT · 2017 to 2019
$1.6M
ROS driven mitochondrial-telomere dysfunction during environmental stressR21ES025606 · NIEHS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI OPRESKO, PATRICIA L, VAN HOUTEN, BENNETT · 2015 to 2016
$414k
JEOL JEM-1011 TRANSMISSION ELECTRON MICROSCOPE: MUSCULAR DYSTROPHYS10RR019003 · NCRR · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI WATKINS, SIMON C · 2004 to 2004
$337k
NCRR NIH HHS RR019003NCRR NIH HHS S10 RR019003NIBIB NIH HHS EB017268NIBIB NIH HHS R01 EB017268NIEHS NIH HHS ES022644NIEHS NIH HHS R01 ES022644NIEHS NIH HHS R21 ES025606NIEHS NIH HHS R33 ES025606
6 · The paper itself

Abstract

Mitochondrial dysfunction is implicated in the pathogenesis of multiple neurological diseases, but elucidation of underlying mechanisms is limited experimentally by the inability to damage specific mitochondria in defined neuronal groups. We developed a precision chemoptogenetic approach to target neuronal mitochondria in the intact nervous system in vivo. MG2I, a chemical fluorogen, produces singlet oxygen when bound to the fluorogen-activating protein dL5** and exposed to far-red light. Transgenic zebrafish expressing dL5** within neuronal mitochondria showed dramatic MG2I- and light-dependent neurobehavioral deficits, caused by neuronal bioenergetic crisis and acute neuronal depolarization. These abnormalities resulted from loss of neuronal respiration, associated with mitochondrial fragmentation, swelling and elimination of cristae. Remaining cellular ultrastructure was preserved initially, but cellular pathology downstream of mitochondrial damage eventually culminated in neuronal death. Our work provides powerful new chemoptogenetic tools for investigating mitochondrial homeostasis and pathophysiology and shows a direct relationship between mitochondrial function, neuronal biogenetics and whole-animal behavior.

Indexed as

Adenosine TriphosphateAnimalsAnimals, Genetically ModifiedBehavior, AnimalElectrophysiologyEmbryo, NonmammalianFluorescent DyesGene Expression RegulationLightMitochondriaMotor ActivityNeuronsOptogeneticsOxygen ConsumptionSingle-Cell AnalysisSpatio-Temporal AnalysisAdenosine TriphosphateFluorescent Dyesbiochemistrycell deathchemical biologychemoptogeneticsmitochondriamotor functionneurosciencerespirationzebrafish

Identifiers

PMID32180546
PMCPMC7077989
OpenAlexW3011257527

What OpenQuestion holds

Textmetadata
LicenceCC0
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 OpenQuestion graph.