Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

ATP Synthase: Mechanism01:48

ATP Synthase: Mechanism

14.3K
In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased...
14.3K
Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

12.5K
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
12.5K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Spaceflight-associated neuro-ocular syndrome (SANS): expert consensus on diagnosis and management.

Eye (London, England)·2026
Same author

CAR T cell therapy selectively depletes disease-driving mutant calreticulin cells in xenotransplants and human organoid models of myelofibrosis.

Science translational medicine·2026
Same author

Atrial cardiomyopathy as a multidomain disease: longitudinal evidence for autonomic remodelling.

Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology·2026
Same author

Interactions of blood biomolecules with early rhythm control in atrial fibrillation patients: Exploratory analysis of the EAST-AFNET 4 Biomolecule Study.

Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology·2026
Same author

Identifying MicroRNA Biomarkers in Idiopathic Intracranial Hypertension: A Pilot Study.

Neurology·2026
Same author

Edoxaban for Stroke Prevention in Atrial Fibrillation in Spain and Portugal: 4-Year Follow-Up of the Observational ETNA-AF-Europe Study.

Journal of clinical medicine·2026
Same journal

Metabolic crisis and TRPM4 activation cause QT prolongation in TANGO2 deficiency disorder.

Cardiovascular research·2026
Same journal

Personalizing Atrial Fibrillation Therapy: Moving from Genetic Association to Mechanistic Translation.

Cardiovascular research·2026
Same journal

Placental Growth Factor Promotes Endothelial Activation and Inflammatory Remodelling in Pulmonary Hypertension.

Cardiovascular research·2026
Same journal

Endothelial-to-mesenchymal transition (EndMT) in atherosclerosis: mechanisms, models and therapies.

Cardiovascular research·2026
Same journal

The gut-heart axis in cardio-oncology.

Cardiovascular research·2026
Same journal

Proteomic signatures as biomarkers of atherosclerosis burden.

Cardiovascular research·2026
See all related articles

Related Experiment Video

Updated: Jun 17, 2025

Phosphorus-31 Magnetic Resonance Spectroscopy: A Tool for Measuring In Vivo Mitochondrial Oxidative Phosphorylation Capacity in Human Skeletal Muscle
09:40

Phosphorus-31 Magnetic Resonance Spectroscopy: A Tool for Measuring In Vivo Mitochondrial Oxidative Phosphorylation Capacity in Human Skeletal Muscle

Published on: January 19, 2017

11.7K

PITX2 deficiency leads to atrial mitochondrial dysfunction.

Jasmeet S Reyat1,2, Laura C Sommerfeld1,3,4,5, Molly O'Reilly1

  • 1Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Wolfson Drive, B15 2TT Birmingham, UK.

Cardiovascular Research
|August 12, 2024
PubMed
Summary
This summary is machine-generated.

Reduced PITX2 in atrial cells impairs mitochondria and shifts metabolism to glycolysis, contributing to atrial fibrillation. This study reveals key mechanisms linking PITX2 deficiency to heart rhythm disorders.

Keywords:
PITX2Atrial fibrillationHuman heart tissueHuman induced pluripotent stem cellsMetabolic shiftMitochondrial dysfunction

More Related Videos

Assessment of Open Probability of the Mitochondrial Permeability Transition Pore in the Setting of Coenzyme Q Excess
07:35

Assessment of Open Probability of the Mitochondrial Permeability Transition Pore in the Setting of Coenzyme Q Excess

Published on: June 1, 2022

2.2K
Treating SCA1 Mice with Water-Soluble Compounds to Non-Specifically Boost Mitochondrial Function
11:47

Treating SCA1 Mice with Water-Soluble Compounds to Non-Specifically Boost Mitochondrial Function

Published on: January 22, 2017

10.5K

Related Experiment Videos

Last Updated: Jun 17, 2025

Phosphorus-31 Magnetic Resonance Spectroscopy: A Tool for Measuring In Vivo Mitochondrial Oxidative Phosphorylation Capacity in Human Skeletal Muscle
09:40

Phosphorus-31 Magnetic Resonance Spectroscopy: A Tool for Measuring In Vivo Mitochondrial Oxidative Phosphorylation Capacity in Human Skeletal Muscle

Published on: January 19, 2017

11.7K
Assessment of Open Probability of the Mitochondrial Permeability Transition Pore in the Setting of Coenzyme Q Excess
07:35

Assessment of Open Probability of the Mitochondrial Permeability Transition Pore in the Setting of Coenzyme Q Excess

Published on: June 1, 2022

2.2K
Treating SCA1 Mice with Water-Soluble Compounds to Non-Specifically Boost Mitochondrial Function
11:47

Treating SCA1 Mice with Water-Soluble Compounds to Non-Specifically Boost Mitochondrial Function

Published on: January 22, 2017

10.5K

Area of Science:

  • Molecular Biology
  • Cardiology
  • Stem Cell Biology

Background:

  • Reduced left atrial PITX2 is linked to atrial cardiomyopathy and atrial fibrillation (AF).
  • The precise mechanisms connecting PITX2 deficiency to AF remain unclear.
  • PITX2 is specifically expressed in left atrial cardiomyocytes (aCMs) in adults.

Purpose of the Study:

  • To elucidate the mechanisms by which PITX2 deficiency leads to atrial fibrillation.
  • To characterize PITX2-deficient human atrial cardiomyocytes derived from induced pluripotent stem cells (hiPSCs).

Main Methods:

  • Generation and characterization of PITX2-deficient human atrial cardiomyocytes (hiPSC-aCMs) and controls.
  • Assessment of sarcomere structure, mitochondrial morphology, and protein expression via electron microscopy.
  • Single-nuclear RNA sequencing to analyze gene expression, focusing on cellular respiration and ion channels.
  • Analysis of mitochondrial respiration and gene expression in human atrial tissue from AF patients.

Main Results:

  • PITX2-deficient hiPSC-aCMs exhibited disorganized sarcomeres, altered mitochondrial content, and dysregulated cellular respiration.
  • A metabolic shift towards increased glycolysis was observed in PITX2-deficient hiPSC-aCMs.
  • PITX2 deficiency led to increased spontaneous beating rates and variable action potential durations in hiPSC-aCMs.
  • Gene expression analysis revealed mitochondrial and metabolic gene dysregulation in human atria associated with AF and reduced PITX2.

Conclusions:

  • PITX2 deficiency directly causes mitochondrial dysfunction and a metabolic shift to glycolysis in human atrial cardiomyocytes.
  • These PITX2-dependent metabolic alterations contribute to the structural and functional cardiac defects observed in PITX2 deficiency.
  • Findings highlight the critical role of PITX2 in maintaining atrial cardiomyocyte metabolic homeostasis and preventing AF.