U.S. Department of Health and Human Services
Olga Protchenko
 

 Contact Info

 
Tel: 301-402-6024
Email: op12g@nih.gov
 

 Select Experience

 
  • Postdoctoral FellowLiver Diseases Section,  NIDDK, NIH2000–2005
  • Ph.D.A.V. Palladin Institute of Biochemistry, National Academy of Science of Ukraine1997
  • M.A.Lviv State University1988
 

 Related Links

 

Olga Protchenko, Ph.D.

Staff Scientist, Genetics and Metabolism SectionLiver Diseases Branch
Specialties
  •  Genetics/Genomics
  •  Molecular Biology/Biochemistry
  • Cell Biology/Cell Signaling
  • Chemistry/Chemical Biology
  • Microbiology/Infectious Diseases (non-viral)
Research Summary/In Plain Language

Research Summary

Research Goal

Our research intends to understand how the body takes up iron, how it is converted into biologically vital forms, and how it is distributed within cells and among organs.  We want to characterize genes and intracellular protein complexes engaged in the trafficking of iron compounds from the site of its synthesis to the cellular organelles where it is used.

Current Research

Heme is an iron-containing protoporphyrin that is important for many biological processes. Because heme is chemically active and can promote oxidative damage of proteins, lipids, and cell structures, it is potentially harmful. There is virtually no “free” heme in the human body due to the potent heme-scavenging system in the blood. At the cellular level, heme homeostasis is a balance of heme production, degradation, and distribution. Mechanisms of heme synthesis and degradation have been intensively studied over the past 60 years. However, the intracellular heme transport pathways are largely unknown and have recently been increasingly recognized as an important area of research. How does the heme, a hydrophobic and potentially toxic compound, get delivered from the site of its synthesis within mitochondria to the heme proteins located in the cytoplasm, intracellular membrane structures, and within organelles? What are the pathways and mechanisms of intracellular heme transport?

To answer these questions, we have employed a model organism, the budding yeast Saccharomyces cerevisiae. When heme synthesis is effective, S. cerevisiae does not take up heme across the plasma membrane. However, heme uptake is significantly induced in yeast under conditions of heme starvation and hypoxia because heme synthesis requires oxygen. We have described inducible heme transport in S. cerevisiae and characterized a yeast porphyrin transporter, Pug1. The yeast system proved to be useful to analyze putative heme transporters from other species. We have employed a heme-deficient strain of S. cerevisiae to characterize the human and worm orthologs of the heme transporters HRG1 and HRG4. Currently, we are conducting studies to identify the proteins important for intracellular heme homeostasis.

To understand changes in cellular iron and heme machinery from health to disease, we combine advantages of different models from yeast to tissue culture and murine studies.​

Applying our Research

Understanding the biology of iron, one of the most essential and abundant microelements in the human body, is vital to develop a treatment for diseases associated with genetic impairment of iron metabolism, such as some forms of anemia and hereditary hemochromatosis. Knowledge of iron homeostasis also gives us an opportunity to help in disorders with secondary impairment of iron metabolism, such as anemia of chronic inflammation, chronic liver inflammation diseases like hepatitis C, and alcoholic liver diseases.

Need for Further Study

In the overview of cellular iron metabolism, the mechanisms and pathways of intracellular transport of iron/heme complexes make up critical parts of the big picture. In fact, this is an important and promising research area. However, at present the questions outnumber answers. Possible mechanisms of heme transfer from mitochondria imply assistance of heme-binding chaperones, organelle-to-organelle fusion, mitophagy, or direct transfer of heme to the target proteins. Designing new yeast reporters to detect these interactions and cells-based assays are some areas to evolve further. Developing higher animal models, such as zebrafish and mice, with targeted “iron genes” is vital for progress in this research area.