Abstract

Intra-mitochondrial Ca is a key signal transducer for energy metabolism. In the heart Ca controls the cyclic contraction, which uses the majority of cellular ATP. As a consequence, it is important to determine whether cytosolic Ca fluctuations are conveyed to the mitochondria. The long-term objective of the proposal is to elucidate the regulation of intracellular Ca in cardiac cells; in the short term the aim is to employ fluorescence microscopy and electrophysiological recording to investigate the role of mitochondria in the regulation of Ca signalling. The working hypothesis is that mitochondrial Ca is heterogeneous, and mitochondria could respond differentially to Ca fluctuations depending on their membrane potential and spatial location.
The specific aims are to determine spatial in-homogeneities in mitochondrial Ca, to assess the ability of mitochondria to transport Ca during changes of cytosolic Ca, and to determine whether there is cross-talk between mitochondria and sarcoplasmic reticulum.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL033333-11
Application #
2735087
Study Section
Physiology Study Section (PHY)
Project Start
1985-07-01
Project End
2000-06-30
Budget Start
1998-07-01
Budget End
1999-06-30
Support Year
11
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
University of Rochester
Department
Pharmacology
Type
Schools of Dentistry
DUNS #
208469486
City
Rochester
State
NY
Country
United States
Zip Code
14627

  Publications

O-Uchi, Jin; Jhun, Bong Sook; Xu, Shangcheng et al. (2014) Adrenergic signaling regulates mitochondrial Ca2+ uptake through Pyk2-dependent tyrosine phosphorylation of the mitochondrial Ca2+ uniporter. Antioxid Redox Signal 21:863-79
O-Uchi, Jin; Ryu, Shin-Young; Jhun, Bong Sook et al. (2014) Mitochondrial ion channels/transporters as sensors and regulators of cellular redox signaling. Antioxid Redox Signal 21:987-1006
Jakob, Regina; Beutner, Gisela; Sharma, Virendra K et al. (2014) Molecular and functional identification of a mitochondrial ryanodine receptor in neurons. Neurosci Lett 575:7-12
Sokolova, Niina; Pan, Shi; Provazza, Sarah et al. (2013) ADP protects cardiac mitochondria under severe oxidative stress. PLoS One 8:e83214
O-Uchi, Jin; Jhun, Bong Sook; Hurst, Stephen et al. (2013) Overexpression of ryanodine receptor type 1 enhances mitochondrial fragmentation and Ca2+-induced ATP production in cardiac H9c2 myoblasts. Am J Physiol Heart Circ Physiol 305:H1736-51
O-Uchi, Jin; Pan, Shi; Sheu, Shey-Shing (2012) Perspectives on: SGP symposium on mitochondrial physiology and medicine: molecular identities of mitochondrial Ca2+ influx mechanism: updated passwords for accessing mitochondrial Ca2+-linked health and disease. J Gen Physiol 139:435-43
Pan, Shi; Ryu, Shin-Young; Sheu, Shey-Shing (2011) Distinctive characteristics and functions of multiple mitochondrial Ca2+ influx mechanisms. Sci China Life Sci 54:763-9
Ryu, Shin-Young; Beutner, Gisela; Kinnally, Kathleen W et al. (2011) Single channel characterization of the mitochondrial ryanodine receptor in heart mitoplasts. J Biol Chem 286:21324-9
Hom, Jennifer R; Quintanilla, Rodrigo A; Hoffman, David L et al. (2011) The permeability transition pore controls cardiac mitochondrial maturation and myocyte differentiation. Dev Cell 21:469-78
Wei, Lan; Salahura, Gheorghe; Boncompagni, Simona et al. (2011) Mitochondrial superoxide flashes: metabolic biomarkers of skeletal muscle activity and disease. FASEB J 25:3068-78

Showing the most recent 10 out of 57 publications