Evidence map›Paper›PMID 29274400›Full record

ArticleMitochondrion2019

Conditional MitoTimer reporter mice for assessment of mitochondrial structure, oxidative stress, and mitophagy.

Rebecca J Wilson, Joshua C Drake, Di Cui, Mei Zhang, Heather M Perry, Jennifer A Kashatus, Christine M Kusminski, Philipp E Scherer, David F Kashatus, Mark D Okusa and 1 more

Open access · hybridAbstract read
In one paragraph

Article in Mitochondrion, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed, 1 pooled it
3.8field-weighted citation impact, top 6% 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

38 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.

  1. Guideline
  2. Review
  3. Review
  4. Article
  5. Article
  6. Targeting mitophagy in neurodegenerative diseases.Nature reviews. Drug discovery · 2025
    Review
  7. Article
  8. Mitochondrial Quality Control.Advances in experimental medicine and biology · 2025
    Review
  9. Article
  10. Article
  11. Imaging immunometabolismImmunometabolism (Cobham, Surrey) · 2024
    Article
  12. Review
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Mitophagy and Neurodegeneration: Between the Knowns and the Unknowns.Frontiers in cell and developmental biology · 2022
    Review
  19. Sensing local energetics to acutely regulate mitophagy in skeletal muscle.Frontiers in cell and developmental biology · 2022
    Review
  20. 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

11 authors at 2 institutions in 1 country.

Rebecca J WilsonDepartment of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA, United States; Center for Skeletal Muscle Research at Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA, United States.
Joshua C DrakeCenter for Skeletal Muscle Research at Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA, United States.
Di CuiCenter for Skeletal Muscle Research at Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA, United States.
Mei ZhangDepartment of Medicine-Cardiovascular Medicine, University of Virginia School of Medicine, Charlottesville, VA, United States; Center for Skeletal Muscle Research at Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA, United States.
Heather M PerryDepartment of Medicine-Nephrology and Center for Immunity, Inflammation, and Regenerative Medicine, University of Virginia School of Medicine, Charlottesville, VA, United States.
Jennifer A KashatusDepartment of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine, Charlottesville, VA, United States.
Christine M KusminskiDepartment of Internal Medicine, UT Southwestern, Dallas, TX, United States.
Philipp E SchererDepartment of Internal Medicine, UT Southwestern, Dallas, TX, United States.
David F KashatusDepartment of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine, Charlottesville, VA, United States.
Mark D OkusaDepartment of Medicine-Nephrology and Center for Immunity, Inflammation, and Regenerative Medicine, University of Virginia School of Medicine, Charlottesville, VA, United States.
Zhen YanDepartment of Medicine-Cardiovascular Medicine, University of Virginia School of Medicine, Charlottesville, VA, United States; Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA, United States; Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville, VA, United States; Center for Skeletal Muscle Research at Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA, United States. Electronic address: zhen.yan@virginia.edu.
University of Virginia · USThe University of Texas Southwestern Medical Center · US

Funding

BASIC CARDIOVASCULAR RESEARCH TRAINING GRANTT32HL007284 · NHLBI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI Brant E Isakson, Gary K Owens · 1985 to 2026
$19.6M
p38 MAPK a regulator of muscle contraction and functionR01AR050429 · NIAMS · VIRGINIA POLYTECHNIC INST AND ST UNIV · PI YAN, ZHEN · 2005 to 2022
$5.3M
Leukocyte Trafficking in Acute Renal FailureR01DK062324 · NIDDK · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI OKUSA, MARK DOUGLAS · 2003 to 2016
$4.4M
Ultrasound for Non-Invasive Prevention of Acute Kidney InjuryR01DK105133 · NIDDK · UNIVERSITY OF VIRGINIA · PI OKUSA, MARK DOUGLAS · 2015 to 2019
$2.4M
Exploring the Role of Mitochondrial Fission in Pancreatic TumorigenesisR01CA200755 · NCI · UNIVERSITY OF VIRGINIA · PI KASHATUS, DAVID FRANCIS · 2016 to 2020
$2.2M
Endothelial sphingosine-1-phosphate receptor 1 regulates renal recovery after acute kidney injuryF32DK108563 · NIDDK · UNIVERSITY OF VIRGINIA · PI PERRY, HEATHER M. · 2015 to 2017
$115k
NCI NIH HHS R01 CA200755NHLBI NIH HHS T32 HL007284NIAMS NIH HHS R01 AR050429NIDDK NIH HHS F32 DK108563NIDDK NIH HHS R01 DK062324NIDDK NIH HHS R01 DK105133
6 · The paper itself

Abstract

Assessment of structural and functional changes of mitochondria is vital for biomedical research as mitochondria are the power plants essential for biological processes and tissue/organ functions. Others and we have developed a novel reporter gene, pMitoTimer, which codes for a redox sensitive mitochondrial targeted protein that switches from green fluorescence protein (GFP) to red fluorescent protein (DsRed) when oxidized. It has been shown in transfected cells, transgenic C. elegans and Drosophila m., as well as somatically transfected adult skeletal muscle that this reporter gene allows quantifiable assessment of mitochondrial structure, oxidative stress, and lysosomal targeting of mitochondria-containing autophagosomes. Here, we generated CAG-CAT-MitoTimer transgenic mice using a transgene containing MitoTimer downstream of LoxP-flanked bacterial chloramphenicol acetyltransferase (CAT) gene with stop codon under the control of the cytomegalovirus (CMV) enhancer fused to the chicken β-actin promoter (CAG). When CAG-CAT-MitoTimer mice were crossbred with various tissue-specific (muscle, adipose tissue, kidney, and pancreatic tumor) or global Cre transgenic mice, the double transgenic offspring showed MitoTimer expression in tissue-specific or global manner. Lastly, we show that hindlimb ischemia-reperfusion caused early, transient increases of mitochondrial oxidative stress, mitochondrial fragmentation and lysosomal targeting of autophagosomes containing mitochondria as well as a later reduction of mitochondrial content in skeletal muscle along with mitochondrial oxidative stress in sciatic nerve. Thus, we have generated conditional MitoTimer mice and provided proof of principle evidence of their utility to simultaneously assess mitochondrial structure, oxidative stress, and mitophagy in vivo in a tissue-specific, controllable fashion.

Indexed as

Genes, ReporterMitophagyOxidative StressAnimalsChloramphenicol O-AcetyltransferaseDisease Models, AnimalGene ExpressionIschemiaLuminescent ProteinsMaleMice, Inbred C57BLMice, TransgenicMitochondriaMuscle, SkeletalPromoter Regions, GeneticChloramphenicol O-AcetyltransferaseLuminescent Proteins

Identifiers

PMID29274400
PMCPMC6387589
OpenAlexW2777266655

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.