Table Of ContentAvraham Mayevsky
Mitochondrial
Function In Vivo
Evaluated by
NADH Fluorescence
Mitochondrial Function In Vivo Evaluated
by NADH Fluorescence
Avraham Mayevsky
Mitochondrial Function
In Vivo Evaluated by NADH
Fluorescence
Avraham Mayevsky
Faculty of Life Sciences
Bar-Ilan University
Ramat-Gan , Israel
ISBN 978-3-319-16681-0 ISBN 978-3-319-16682-7 (eBook)
DOI 10.1007/978-3-319-16682-7
Library of Congress Control Number: 2015938388
Springer Cham Heidelberg New York Dordrecht London
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This book is dedicated to my dearest wife, Zipora, for her vision, patience,
and support for more than fi ve decades. Without her encouragement,
my academic achievements and writing this book would have been
impossible to accomplish.
Pref ace
This book is not a biography of my life: rather, it tells the story of my research activities since
my post-doctorate training with Prof. Britton Chance at the University of Pennsylvania,
Philadelphia. In this book, I am integrating the knowledge of all scientists, including myself
and my research group, who investigated the function of the intracellular organelle—the mito-
chondrion—under in vivo conditions.
N ormal mitochondrial function is an essential factor in all tissues and organs in the body.
Mitochondrial activity provides all cells in the body with the energy source (ATP) to enable
normal functions. Mitochondrial dysfunction creates a major pathological state in various
organs because of the decrease in this energy source (ATP). Much pathology in the human
body is related to dysfunction of the mitochondria and decrease in ATP production.
One of the options for evaluating mitochondrial function in vivo is to measure the autofl uo-
rescence of the NADH molecule bound to the enzymatic system in the respiratory chain
embedded in the mitochondria. This approach to monitor the mitochondria in vivo was started
in the early 1950s by the late Prof. Britton Chance from the University of Pennsylvania,
Philadelphia. More than 800 papers were published in this research area by various investiga-
tors around the world.
Most of the studies involved experimental animals, using various protocols, mimicking the
pathological state in patients. In the past 20 years, the same methodology has been applied to
monitor patients under various pathological states.
During the years, I realized that many young graduate students or other scientists who try
to enter this specifi c fi eld of research have diffi culties in fi nding the appropriate source of
information to perform a well-controlled study using NADH fl uorescence monitoring in vivo.
For this reason, I decided to integrate all the relevant information in a book that will be avail-
able to all newcomers to this specifi c fi eld of research, that of mitochondrial function in vivo.
This is the fi rst time that this subject has been described in detail, citing almost all the papers
published in this fi eld.
The fi rst two chapters are a general introduction to the signifi cance of mitochondrial func-
tion in health and disease, as well as its part in tissue energy metabolism. Chapter 3 contains a
historical overview of NADH monitoring ranging from isolated mitochondria in vitro to intact
organs in vivo. As I found many years ago, all optical techniques, and especially monitoring of
NADH fl uorescence, when applied to in vivo conditions are very sensitive to the appropriate
performance of the experimental procedures. Therefore, all the important technological aspects
of NADH monitoring are presented in great detail in Chap. 4 .
After the development of the fi ber-optic-based fl uorometer, I realized as a physiologist that
monitoring of NADH alone would not provide enough information to understand the patho-
physiology of organs in vivo. Therefore, I developed the multiparametric monitoring approach
enabling measurement, in addition to NADH fl uorescence, of other physiological parameters
at the tissue level in vivo. Chapter 5 is devoted to this subject. In Chap. 6 , the ability to measure
NADH as well as other parameters from more than one site simultaneously is presented.
In Chapter 7 , which is the largest chapter in the book, I accumulated all the information
regarding the responses of NADH as well as other parameters to various perturbations induced
in various organs of experimental animals. Most of the results in NADH monitoring were
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viii Preface
accumulated in brain studies; therefore, I selected most of the figures from those studies.
In each subject, I started with a few representative results published by other researchers,
followed by my own studies. It is important to note that in all studies describing the responses
of NADH to various perturbations, a typical analog tracing of the responses is presented in
parallel to the quantitative analysis of the results and its statistical analysis. I decided to present
mainly the real-time results that appeared on paper recorders or were accumulated by comput-
erized systems.
T o help the reader to fi nd relevant results to the new studies, I prepared appropriate tables,
presented in Chap. 8 , that classifi ed all the data accumulated according to the animal or organ
selected as well as according to the perturbations used.
I n Chap. 9, the use of NADH monitoring in various organs of the human body are presented
in historical perspectives and with the up-to-date technology developed during the past 10 to
20 years.
In the last chapter, Chap. 1 0 , a short discussion and future perspectives are presented.
Ramat-Gan, Israel Avraham Mayevsky
Acknowledgments
I dedicate this book to my four children, Amotz, Sarit, Hagit, and Shalev, who understood my
devotion to an unusual career and enabled me to fulfi ll all my obligations and academic
activities.
My deep appreciation is given to my parents, Shabtai and Rachel Mayevsky, for their devo-
tion and support throughout my life.
My appreciation is given to the late Prof. Britton Chance, an outstanding scientist, teacher,
and colleague, for almost four decades of fruitful collaboration.
During the 40 years of research activities at Bar Ilan University I trained many M.Sc. and
Ph.D. students. I want to thank all of them for their confi dence and their efforts during the
experimental work as well as in preparation and publication of the manuscripts.
Special appreciation is given to a few of my graduate students who joined my research team
after their graduation. Their assistance in training new undergraduate and graduate students is
appreciated very much. Nili Zarchin, M.Sc., joined my laboratory in the early 1980s. Judith
Sonn, Ph.D., started her activities in my laboratory in the early 1990s. Efrat Barbiro-Michaeli,
Ph.D., started her activities in the mid-1990 and collaborated with me until my nomination as
Professor Emeritus at Bar Ilan University a few years ago. During the past few years, she took
part in the preparation for writing this book, and her help is appreciated.
P rof. Gennady Rogatsky immigrated to Israel in the early 1990s and was active in my labo-
ratory until his retirement. He was involved in research activities and helped me to establish
the literature classifi cation for this book. My appreciation is given to his contributions.
Special thanks and deep appreciation are given to Eli Zimerman, from Bar Ian University,
for his long-term support in the development and maintenance of various instruments in my
laboratory that enabled us to perform our studies.
I want to thank Mrs. Avrille Goldreich, from the Faculty of Life Sciences at Bar Ian
University, for her many years of help and support in the preparation of my manuscripts and
especially this book.
F inally yet importantly, I express my sincere gratitude to Yossi Mor, who introduced me to
Jack Lahav, Co-Chairmen of Israel Venture Partners. This team is supporting me to translate
the science described in this book into a revolutionary medical device that will improve the
health of humankind.
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