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 Experiment Videos

Targeting proteins to mitochondria using TAT.

Victoria Del Gaizo1, James A MacKenzie, R Mark Payne

  • 1Division of Molecular Medicine, Department of Internal Medicine, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1081, USA.

Molecular Genetics and Metabolism
|October 22, 2003
PubMed
Summary
This summary is machine-generated.

Related Concept Videos

You might also read

Related Articles

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

Sort by
Same author

Low Albumin and Elevated FIB-4 Are Associated With Adverse Outcomes After the Fontan Procedure.

Heart, lung & circulation·2026
Same author

Ex Vivo Effect of Apixaban on Hemostatic Biomarkers in Children With Heart Disease: A SAXOPHONE Trial Substudy.

Journal of the American Heart Association·2026
Same author

Positron emission tomography reveals increased myocardial glucose uptake in a subset of Friedreich ataxia patients.

Scientific reports·2025
Same author

Mitigation of Radiation-induced Cardiotoxicity by Subcutaneous "Protective Wounding".

Radiation research·2025
Same author

Longitudinal Intracardiac Right Ventricular Flow Analysis in Infants With Hypoplastic Left Heart Syndrome in Interstage I Using Novel Doppler Velocity Reconstruction.

Journal of the American Heart Association·2025
Same author

Revisiting the Effect of Udenafil on Exercise Performance in Patients With Fontan Circulation: Results of a Post Hoc Analysis of the FUEL Trial.

Journal of the American Heart Association·2025
Same journal

Accessibility and harmonization of biochemical tests for diagnosis and monitoring of Porphyrias in the United States: Recommendations by members of the American Porphyrias Expert Collaborative (APEX).

Molecular genetics and metabolism·2026
Same journal

Participants with long-chain 3-hydroxy-acylCoA dehydrogenase deficiency (LCHADD)/trifunctional protein deficiency (TFPD) report consistent low-fat diet intake over time.

Molecular genetics and metabolism·2026
Same journal

Expanding the clinical and molecular spectrum of NGLY1 deficiency: A multicenter cohort.

Molecular genetics and metabolism·2026
Same journal

Driving treatment for females with X-linked adrenoleukodystrophy.

Molecular genetics and metabolism·2026
Same journal

High dietary fat causes muscle structural breakdown, mitochondrial dysfunction, and contractile deficits in the absence of carnitine palmitoyltransferase 2.

Molecular genetics and metabolism·2026
Same journal

Ketogenic diet therapy in pyruvate dehydrogenase deficiency: Global clinical practice from literature and survey data.

Molecular genetics and metabolism·2026
See all related articles

Mitochondrial protein therapies using TAT fusion proteins can enter cells and mitochondria independently of the normal import pathway. Adding a mitochondrial targeting sequence (MTS) ensures their persistence for potential therapeutic applications.

Area of Science:

  • Mitochondrial biology
  • Protein transduction
  • Gene therapy research

Background:

  • Mitochondrial dysfunction leads to severe human diseases.
  • Current treatments for mitochondrial defects are biochemical, not gene-based.
  • Novel strategies are needed for targeted mitochondrial repair.

Purpose of the Study:

  • To investigate the ability of TAT fusion proteins to cross mitochondrial membranes.
  • To determine if a mitochondrial targeting sequence (MTS) enhances protein persistence within mitochondria.
  • To evaluate the potential of TAT-MTS fusion proteins as mitochondrial therapies.

Main Methods:

  • Utilized TAT-GFP and TAT-mMDH-GFP fusion proteins.
  • Assessed protein protection from protease with isolated mitochondria.

Related Experiment Videos

  • Examined cellular uptake and mitochondrial transduction in cultured cells.
  • Investigated protein persistence with and without MTS.
  • Tested transduction under conditions of disrupted mitochondrial import pathways.
  • Administered TAT-mMDH-GFP to pregnant mice to assess in vivo distribution.

    • Main Results:

    • TAT fusion proteins were protected from protease and transduced into isolated mitochondria.
    • Both TAT-GFP and TAT-mMDH-GFP rapidly entered cultured cells and mitochondria.
    • MTS was essential for processing and long-term persistence of fusion proteins in mitochondria.
    • Protein transduction occurred independently of mitochondrial import receptors, membrane potential, or pH gradients.
    • In vivo, TAT-mMDH-GFP was detected in fetal and neonatal pups after maternal injection.

    Conclusions:

    • TAT fusion proteins can bypass conventional mitochondrial import mechanisms.
    • The MTS is crucial for sustained presence of therapeutic proteins within mitochondria.
    • TAT-MTS fusion proteins show promise as a novel approach for mitochondrial protein replacement therapy.