We will examine how eukaryotic mitochondria adapt to hypoxia using the yeast, Saccharomyces cerevisiae. Mitochondria from anaerobically grown S. cerevisiae are enlarged compared to mitochondria from aerobically grown cells. They also lack cytochromes, and are respiration- deficient. Similar changes are observed in mammalian mitochondria, particularly in mitochondria from ischemic hearts. Little is known about the molecular mechanisms regulating changes in mitochondrial structure and function in response to hypoxia. in addition, not much is known about how mitochondria function at oxygen levels between normoxia and hypoxia. These questions will be addressed in our proposed research. First, it will be determined how mitochondrial structure and function are affected by hypoxia, and at oxygen concentrations between normoxia and hypoxia. Second, proteins will be identified that regulate changes in mitochondrial structure and function in response to hypoxia. Third, it will be determined how genes that control mitochondrial structure and function, including OLE1, are regulated by oxygen. Specifically, it will be determined if either heme or reactive oxygen species (ROS) are involved in gene regulation. This research will provide insight into how mitochondria are affected by both hypoxia and ischemia.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32HL010449-02
Application #
6402757
Study Section
Special Emphasis Panel (ZRG1-BIO (02))
Program Officer
Commarato, Michael
Project Start
2001-08-08
Project End
Budget Start
2001-08-08
Budget End
2002-08-07
Support Year
2
Fiscal Year
2001
Total Cost
$34,832
Indirect Cost
Name
University of Colorado at Boulder
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
City
Boulder
State
CO
Country
United States
Zip Code
80309
Starr, D A; Hermann, G J; Malone, C J et al. (2001) unc-83 encodes a novel component of the nuclear envelope and is essential for proper nuclear migration. Development 128:5039-50