Evidence map›Paper›PMID 25447550›Full record

ArticleBiochimica et biophysica acta2015

Quantitative analysis of mitochondrial morphology and membrane potential in living cells using high-content imaging, machine learning, and morphological binning.

Anthony P Leonard, Robert B Cameron, Jaime L Speiser, Bethany J Wolf, Yuri K Peterson, Rick G Schnellmann, Craig C Beeson, Bärbel Rohrer

Open access · greenAbstract read
In one paragraph

Article in Biochimica et biophysica acta, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.

0numbers the graph read from it
0cells of the map it votes in
82citing papers in PubMed
3.4field-weighted citation impact, top 7% 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

82 citing papers in PubMed, 150 citations in OpenAlex.

  1. Tau protein as a regulator of mitochondrial function and dynamics.Proceedings of the National Academy of Sciences of the United States of America · 2026
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22 more citing papers are in PubMed but not listed here.

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

8 authors at 2 institutions in 1 country.

Anthony P LeonardDept. of Ophthalmology, Medical University of South Carolina, USA; Dept. of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, USA.
Robert B CameronDept. of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, USA.
Jaime L SpeiserDept. of Public Health Sciences, Medical University of South Carolina, USA.
Bethany J WolfDept. of Public Health Sciences, Medical University of South Carolina, USA.
Yuri K PetersonDept. of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, USA.
Rick G SchnellmannDept. of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, USA.
Craig C BeesonDept. of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, USA.
Bärbel RohrerDept. of Ophthalmology, Medical University of South Carolina, USA; Ralph H. Johnson Memorial Veteran's Administration Hospital, USA.
Medical University of South Carolina · USUnited States Department of Veterans Affairs · US

Funding

TRAINING TO IMPROVE CARDIOVASCULAR THERAPIEST32HL007260 · NHLBI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI MENICK, DONALD R. · 1985 to 2021
$11.1M
SOUTH CAROLINA CLINICAL & TRANSLATIONAL RESEARCH INSTITUTE (SCTR)UL1RR029882 · NCRR · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI BRADY, KATHLEEN T. · 2009 to 2011
$10.1M
South Carolina Clinical & Translational Research Institute (SCTR)UL1TR000062 · NCATS · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI BRADY, KATHLEEN T. · 2012 to 2014
$9.4M
TRAINING PROGRAM FOR MEDICAL SCIENTISTST32GM008716 · NIGMS · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI DEMORE, NANCY · 1999 to 2024
$9.3M
Mitochondrial Biogenesis Promotes Recovery From Oxidant InjuryR01GM084147 · NIGMS · UNIVERSITY OF ARIZONA · PI SCHNELLMANN, RICK G · 2008 to 2016
$2.4M
Alternative Pathway of Complement Activation in Age-Related Macular DegenerationR01EY019320 · NEI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI ROHRER, BAERBEL · 2010 to 2014
$2.1M
MUSC FACIL EXPANSION &RENOV: SLE C06RR015455 · NCRR · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI RAYMOND, JOHN R · 2002 to 2002
$2.0M
High Throughput Mitochondrial Nephrotoxicant AssayR44ES019378 · NIEHS · MITOHEALTH, INC. · PI BEESON, CRAIG CANO · 2011 to 2012
$1.6M
South Carolina Clinical & Translational Research Institute (SCTR)TL1RR029881 · NCRR · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI BRADY, KATHLEEN T. · 2009 to 2011
$1.1M
ECT Implants for Factor H Delivery in Models of AMDR01EY024581 · NEI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI ROHRER, BAERBEL · 2014 to 2016
$1.1M
South Carolina Clinical & Translational Research Institute (SCTR)TL1TR000061 · NCATS · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI BRADY, KATHLEEN T. · 2012 to 2014
$483k
Inducers of Mitochondrial BiogenesisR43GM097770 · NIGMS · MITOHEALTH, INC. · PI BEESON, CRAIG CANO · 2011 to 2011
$312k
BLRD VA I01 BX000851BLRD VA I01 BX003050NCATS NIH HHS TL1 TR000061NCATS NIH HHS UL1 TR000062NCRR NIH HHS C06 RR015455NCRR NIH HHS S10 RR027122NCRR NIH HHS TL1 RR029881NCRR NIH HHS UL1 RR029882NEI NIH HHS R01 EY019320NEI NIH HHS R01 EY019320 -01A1NEI NIH HHS R01 EY024581NHLBI NIH HHS T32 HL007260NIDDK NIH HHS F30 DK104550NIEHS NIH HHS R43 ES019378NIEHS NIH HHS R44 ES019378NIGMS NIH HHS R01 GM084147NIGMS NIH HHS R43 GM097770NIGMS NIH HHS T32 GM008716PHS HHS 084147RRD VA I01 RX000444
6 · The paper itself

Abstract

Understanding the processes of mitochondrial dynamics (fission, fusion, biogenesis, and mitophagy) has been hampered by the lack of automated, deterministic methods to measure mitochondrial morphology from microscopic images. A method to quantify mitochondrial morphology and function is presented here using a commercially available automated high-content wide-field fluorescent microscopy platform and R programming-language-based semi-automated data analysis to achieve high throughput morphological categorization (puncta, rod, network, and large & round) and quantification of mitochondrial membrane potential. In conjunction with cellular respirometry to measure mitochondrial respiratory capacity, this method detected that increasing concentrations of toxicants known to directly or indirectly affect mitochondria (t-butyl hydroperoxide [TBHP], rotenone, antimycin A, oligomycin, ouabain, and carbonyl cyanide-p-trifluoromethoxyphenylhydrazone [FCCP]), decreased mitochondrial networked areas in cultured 661w cells to 0.60-0.80 at concentrations that inhibited respiratory capacity to 0.20-0.70 (fold change compared to vehicle). Concomitantly, mitochondrial swelling was increased from 1.4- to 2.3-fold of vehicle as indicated by changes in large & round areas in response to TBHP, oligomycin, or ouabain. Finally, the automated identification of mitochondrial location enabled accurate quantification of mitochondrial membrane potential by measuring intramitochondrial tetramethylrhodamine methyl ester (TMRM) fluorescence intensity. Administration of FCCP depolarized and administration of oligomycin hyperpolarized mitochondria, as evidenced by changes in intramitochondrial TMRM fluorescence intensities to 0.33- or 5.25-fold of vehicle control values, respectively. In summary, this high-content imaging method accurately quantified mitochondrial morphology and membrane potential in hundreds of thousands of cells on a per-cell basis, with sufficient throughput for pharmacological or toxicological evaluation.

Indexed as

Artificial IntelligenceMembrane Potential, MitochondrialAnimalsCarbonyl Cyanide m-Chlorophenyl HydrazoneCell LineCell MembraneCell RespirationCell SurvivalElectron TransportImaging, Three-DimensionalMiceMitochondriaOxidantsPhenotypeSodium-Potassium-Exchanging ATPaseStress, Physiologicalcarbonylcyanide 4-trifluoromethoxyphenylhydrazoneCarbonyl Cyanide m-Chlorophenyl HydrazoneOxidantsSodium-Potassium-Exchanging ATPasetert-ButylhydroperoxideHigh content microscopyImage cytometryMitochondrial dynamicsMitochondrial functionMitochondrial toxicologyMorphometry

Identifiers

PMID25447550
PMCPMC4289477
OpenAlexW2044998619

What OpenQuestion holds

Textmetadata
LicenceTDM
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.