The number of identified human degenerative diseases with involvement of mitochondrial malfunction is steadily increasing. Therefore, the need for a detailed understanding of the physiologic controls of mitochondrial function in the living cell has become urgent. The experiments and analyses proposed in this application aim to develop a quantitative and integrated understanding of mitochondrial performance in the living cell, with emphasis on the sensitivity to cytosolic (ADP), to metabolic state influenced by the type of substrate, and to altered cytosolic (Ca++). Non-invasive spectroscopic and oxygen polarographic measurements of mitochondrial function will be made in excised mouse EDL (fast-twitch) and SOL (slow-twitch) muscles at rest and during contractile activity. The mitochondrial (ADP) response functions will be determined under control and physiologically and pharmacologically altered conditions. Completion of the stated aims will establish a paradigm for approaching similar quantitative questions in other cells and tissues. Further, the energy balance algorithm developed will provide a general predictive and analytical tool in the study of cell energetics and the relation to normal cell function and disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
2R01AR036281-15
Application #
6044773
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Program Officer
Lymn, Richard W
Project Start
1988-10-01
Project End
2005-03-31
Budget Start
2000-04-01
Budget End
2001-03-31
Support Year
15
Fiscal Year
2000
Total Cost
$429,473
Indirect Cost
Name
University of Washington
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
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Marcinek, David J; Schenkman, Kenneth A; Ciesielski, Wayne A et al. (2005) Reduced mitochondrial coupling in vivo alters cellular energetics in aged mouse skeletal muscle. J Physiol 569:467-73

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