MITOCHONDRIAL FUNCTION AND TISSUE VIABILITYIN VIVO: FROM ANIMAL EXPERIMENTS TO CLINICAL APPLICATIONS. FORTY YEARS OF FRUITFUL COLLABORATION WITH BRITTON CHANCE

Abstract

The involvement of mitochondrial dysfunction in many pathophysiological conditions and human diseases is well documented. In order to evaluate mitochondrial function in vitro, many experimental systems have been developed. Nevertheless the number of in vivo monitoring systems for the evaluation of mitochondrial activities in intact animals and patients is relatively limited. The pioneering development of the conceptual and technological aspects of mitochondrial monitoring, in vitro and in vivo, was done by the late Prof. Britton Chance (July 24, 1913–November 16, 2010) since the early 1950s. It was my privilege to join his laboratory in 1972 and collaborate with him for almost four decades. The main achievements of our collaboration are presented in this paper. Our activities included cycles of technology development, followed by its applications to study various pathophysiological conditions. In the initial stage, the first fiber-optic–based NADH fluorometer was developed. This device enabled us to monitor various organs in anesthetized animals as well as the brain of nonanesthetized small animals. Later on, the addition of various physiological parameters to NADH monitoring enabled us to correlate mitochondrial function with other cellular functions. The application of the developed technology to clinical situations was a major interest of Prof. Chance and indeed this goal was achieved in the last decade. As of today, the basic tool for NADH monitoring and the large database of results are available for large-scale experimental and clinical applications.

Refractory Period Modulates the Spatiotemporal Evolution of Cortical Spreading Depression: A Computational Study

“…To mimic the spatiotemporal pattern of CSD waves characterized in experments, this model was specified with two space dimensions simulation [30] rather than the one space dimension studies [34] – [36] . And, this study focused on a series of CSD waves [37] , [38] , not just on a solitary one [34] , [36] , [39] , [40] . Further more, the varying spatiotemporal evolutions of CSD waves cannot be explained by the influence of the cortex geometry [20] , [21] but by the refractory period in this work.…”

mBeRFP, an Improved Large Stokes Shift Red Fluorescent Protein

“…Therefore, mBeRFP and mCerulean can be simultaneously imaged in a single cell for long-term imaging experiments without the need to reset the imaging software parameters during signal acquisition. To dynamically image two molecules, we fused mBeRFP with a mitochondrial localization sequence and mCerulean (a CFP variant) with Bax, which is a proapoptotic member of the Bcl-2 family and translocates to discrete foci on mitochondria during the initial stages of apoptosis [22], [23]. After the cells were co-transformed with the two constructs and exposed to 30 µg/mL cisplatin for 8 h, we observed four discrete Bax distribution patterns (Figure 4C).…”

Correction: Refractory Period Modulates the Spatiotemporal Evolution of Cortical Spreading Depression: A Computational Study

“…To mimic the spatiotemporal pattern of CSD waves characterized in experments, this model was specified with two space dimensions simulation [30] rather than the one space dimension studies [34][35][36]. And, this study focused on a series of CSD waves [37,38], not just on a solitary one [34,36,39,40]. Further more, the varying spatiotemporal evolutions of CSD waves cannot be explained by the influence of the cortex geometry [20,21] but by the refractory period in this work.…”