The purpose of these studies is to establish a better understanding of the energy metabolism of biological tissues. Towards this goal, the laboratory concentrates on the use of screening approaches in proteomics and post-translational modifications. The following major findings were made over the last year: 1) With regard to nuclear and mitochondrial protein programming of heart function. We have established that the left and right heart ventricles are programmed identically, that is the protein content for over 1000 proteins is essentially the same in the right heart and left heart despite the fact that these two structures have vastly different workloads (afterload pressure 5 times different), different embryological origins and serve different vascular beds(pulmonary versus body). This observation that the ratio of metabolic enzymes and contractile elements are in a fixed in the mammalian right and left heart as well as across most mammalian species suggest that this ratio has been optimized for the continuous contractile activity of the heart. That is, in the fixed compartment of the cell there is a unique solution the balance of space available for the metabolic machinery and the contractile elements. Supporting this notion was the demonstration that the metabolic stress of the right heart increases much faster than the left heart ventricle, extrapolating this data reveals that at maximum workloads the right heart is working as hard as the left heart. These data also suggest that the steeper relationship between workload and metabolic stress in the right heart might be the source of the apparent increased sensitivity of the right heart to hypertrophy under different stressed conditions. 2) A hypothesis has been developed that tissues with large swings in metabolic activity (i.e. heart and muscle) hold mitochondrial electron transport activity in reserve via post translational modifications while more constant activity tissues (i.e. liver) have most of their enzymatic activity active and available. To evaluate the hypothesis we have demonstrated that the heart mitochondrial enzymes are suppressed at rest in the heart, in vivo and are reversibly activated by the infusion of dobutamine. These studies demonstrate for the first time that the Complexes of oxidative phosphorylation are dynamically modulated in the intact heart by workload. The mechanism of this acute modulation of activity is currently under investigation with a working hypothesis that this effect is generated by more ancient bacterial post-translational modification systems within the mitochondria. The implications of this study with regard to heart failure, hibernation, cardioplegia and other clinical conditions are currently being explored. 3) The location and dynamics of mitochondria within a cell is believed to play an important role in the programming of mitochondrial function along with the protein that is inserted. Working with the investigators from NICHD we have developed a transgenetic mouse line that has a photo convertible fluorescent protein inside the mitochondrial. This protein normal fluorescence occurs in the green, however once it has been treated with UV light it converts to a red fluorescence. This permits labeling of specific pools within an animal and monitoring the movement and potential fusion events in vivo. The imaging methods to conduct these studies in vivo are being developed in another project within the laboratory

Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
National Heart, Lung, and Blood Institute
Zip Code
Kuzmiak-Glancy, Sarah; Covian, Raúl; Femnou, Armel N et al. (2018) Cardiac performance is limited by oxygen delivery to the mitochondria in the crystalloid-perfused working heart. Am J Physiol Heart Circ Physiol 314:H704-H715
Liu, Fan; Lössl, Philip; Rabbitts, Beverley M et al. (2018) The interactome of intact mitochondria by cross-linking mass spectrometry provides evidence for coexisting respiratory supercomplexes. Mol Cell Proteomics 17:216-232
Tarasenko, Tatyana N; Pacheco, Susan E; Koenig, Mary Kay et al. (2017) Cytochrome c Oxidase Activity Is a Metabolic Checkpoint that Regulates Cell Fate Decisions During T Cell Activation and Differentiation. Cell Metab 25:1254-1268.e7
Nielles-Vallespin, Sonia; Khalique, Zohya; Ferreira, Pedro F et al. (2017) Assessment of Myocardial Microstructural Dynamics by In Vivo Diffusion Tensor Cardiac Magnetic Resonance. J Am Coll Cardiol 69:661-676
Femnou, Armel N; Kuzmiak-Glancy, Sarah; Covian, Raul et al. (2017) Intracardiac light catheter for rapid scanning transmural absorbance spectroscopy of perfused myocardium: measurement of myoglobin oxygenation and mitochondria redox state. Am J Physiol Heart Circ Physiol 313:H1199-H1208
Patel, Keval D; Glancy, Brian; Balaban, Robert S (2016) The electrochemical transmission in I-Band segments of the mitochondrial reticulum. Biochim Biophys Acta 1857:1284-1289
Vinnakota, Kalyan C; Cha, Chae Y; Rorsman, Patrik et al. (2016) Improving the physiological realism of experimental models. Interface Focus 6:20150076
Murphy, Elizabeth; Ardehali, Hossein; Balaban, Robert S et al. (2016) Mitochondrial Function, Biology, and Role in Disease: A Scientific Statement From the American Heart Association. Circ Res 118:1960-91
Chen, Zhe; Qi, Yun; French, Stephanie et al. (2015) Genetic mosaic analysis of a deleterious mitochondrial DNA mutation in Drosophila reveals novel aspects of mitochondrial regulation and function. Mol Biol Cell 26:674-84
Kooragayala, Keshav; Gotoh, Norimoto; Cogliati, Tiziana et al. (2015) Quantification of Oxygen Consumption in Retina Ex Vivo Demonstrates Limited Reserve Capacity of Photoreceptor Mitochondria. Invest Ophthalmol Vis Sci 56:8428-36

Showing the most recent 10 out of 40 publications