Developments in Molecular and Cellular Biochemistry – serie

During recent decades, bewildering progress has occurred in the field of Molecular and Cellular Biochemistry. Progress has been extraordinarily rapid primarily because of the challenge for finding solutions to a wide variety of diseases and the availability of new techniques for monitoring biochemical processes. This has resulted in a voluminous and complex literature in the field of biochemical medicine so that there is a clear need for the synthesis and analysis of the continuing expansion of valuable data. It was thus considered appropriate to initiate a new series of monographs, each dedicated to a specialized area of investigation, encompassing molecular and cellular processes in health and disease. Most of the biochemical scientists have devoted their energies in understanding the fundamentals of biochemistry and indeed impressive advances have been made in the past. However, the full potential for explanation has been hampered by the concept of universality of biochemical reactions occurring in the cell. In view of the fact that each organ in the body performs a distinct function, it is now beginning to be realized that each cell type is unique in its need to survive and perform its specific function. Accordingly, the aspect of individualty is receiving increased attention for revealing new avenues in the study of pathophysiology of cellular abnormalities.

The discovery of the second-messenger functions of on serine and threonine residues. Although there is inositol 1,4,5-trisphosphate (Ins(1 ,4,5)P 3) and 1,2-dia- general agreement that PKC plays an important role in cylglycerol (DAG), the products of receptor-stimulated the initiation and/or modulation of receptor-linked re- phosphatidylinositol 4,5-bisphosphate (PtdIns( 4,5)P ) 2 sponses, the precise nature or molecular details of this hydrolysis, marked a turning point in the studies on the involvement remain elusive. There are several sugges- mechanisms of mediation of functional hormone and tions of possible functions of PKC, including involve- neurotransmitter responses. The historical background ment in modulation of ionconductance, regulation of of this discovery and the extensive bibliography of the receptor interaction with components of (other) signal 2 enormously expanding knowledge in this field was re- transduction pathways, modulation of Ca + sensitivity cently presented by Rana and Hokin [1], the latter of contractile proteins and gene expression [6]. author who first observed the 'phosphoinositide' effect The receptors involved in the activation of the adeny- 35 years ago.It was, however, the Ca2+ gating hypothe- late cyclase and PtdIns cascade pathways have one com- sis proposed by Michell [2] on basis of a survey of mon feature. They are present in the plasmamembrane observations on the phosphoinositide turnover in a as complexes with GTP binding proteins (G-proteins).

A variety of metabolic processes are known to be intimately involved in the maintenance of cellular structure and function. lt has also become clear that metabolic events involved in the synthesis and hydrolysis of ATP as well as for the synthesis of proteins and phospholipids are essential for cellular health. The regulation of cell function is generally achieved through participation of a wide variety of hormones and different signal transduction mechanisms for the activation/deactivation of some specific metabolic processes. In this regard cyclic AMP and calcium seem to play a crucial role. Various hormones are also known to affect the genetic machinery of all the cell; however, the exact signals for genetic control of cellular function are not well defined. In particular, the sequence of events concerned with remodelling of different types of cells under various pathological situations is poorly understood. In this book we have therefore dealt with some of these issues from biochemical, molecular biological, physiological, and pharmacological viewpoints.Special emphasis has been laid on understanding heart function and metabolism in health and disease in general, and cardiac hypertrophy, heartfailure, and ischemic heartdisease in particular. It is hoped that this multidisciplinary information will be of value to basic scientists and clinical investigators.

The cellular functions of lipid-transport proteins cannot can be obtained, as well as structural information re- garding the local environment of the spectroscopic be fully realized without a comprehensive knowledge of probe. However, changes in protein fluorescence upon their binding properties. In particular, it is important to identify physiologically important ligands and establish ligand binding are sometimes too small to quantitate. their binding affinities, stoichiometries and specificities. This is particularly true for L-FABP, which has no tryp- Since many lipid-binding proteins exhibit no enzymatic tophan residues. Also, some lipids lack intrinsic fluores- cence or paramagnetic properties, including many lipids activity, binding parameters provide an important quan- titative measure for comparing the 'activity' of various of physiological interest. In such cases, lipid analogues wild-type and mutant forms. For this purpose, binding containing structure-perturbing anthroylxoxy or doxyl assays that are quantitative, accurate and robust are de- probes are required. Lipids that do have intrinsic fluor- sirable. escence, such as parinaric acid, are labile and prone to For the intracellular fatty acid- and lipid-binding pro- oxidation.The binding of native ligands can be moni- teins, a variety of biochemical and biophysical binding tored by isotope-directed NMR techniques, provided assays have been used. The biochemical assays include that enrichment with 13C or another suitable isotope is those based on gel-filtration [1-3], equilibrium dialysis feasible. Although such NMR methods are useful for de- [4], Lipidex [5,6] and liposomes [7].

2 During our formative years with Dr. Krebs at Davis, ed until the ER becomes substantially depleted of Ca +. California, we (c. and M. Brostrom) were imbued with For example, acute exposure of GH3 pituitary cells to 2 2 our continuing interest in the roles of Ca+ and cAMP in Ca+ ionophore A23187 or EGTA has been found to re- biological control mechanisms. We remember our time sult in the inhibition of amino acid incorporation. disap- with Dr. Krebs with great affection both for his intense pearance of polysomal content with accumulation of interest and high standards in science and for his great monosomes and ribosomal subunits. sharp reduction of decency in the treatment of postdoctoral fellows. We the cellular content of 43S pre initiation complex. and have subsequently aspired, within the constraints of our the phosphorylation of elF-2ex and inhibition of eIF-2B ability, to pattern our behavior in accord with this expe- [15-17]. Neither translational elongation nor peptide rience.Our current research involving the control of chain termination appeared to be affected in these ex- protein synthesis at mRNA translation embodies much periments, since average ribosomal transit times and the methionylation of tRNA;met were not altered. Amino of the familiar in protein phosphorylation with some new twists that we shall highlight in this article with our acid incorporation was unaffected during the period of 2 associate. Dr. Prostko. Ca+ release prior to suppression of initiation.

Considering the current interest in cellular regulation and intracellular signalling systems, it is surprising that the contribution of ADP-ribosylation reactions to the modulation of a variety of specific cell processes, in parallel with other post-translational modifications such as phosphorylation, has not been generally recognized. While it is not feasible to cover all aspects of ADP-ribosylation, the thirty-one articles contained in this volume provide an overview of recent progress in the field within the context of cell control mechanisms. For the convenience of the reader, the various topics have been grouped into several sections: (a) poly(ADP-ribosyl)ation; (b) mono-ADP-ribosylation; (c) toxin mono-ADP-ribosylation; (d) inhibitors and activators; (e) protein modification with ADP-ribose and its analogues; and (f) non-modification forms of ADP-ribose. The contents of the individual chapters reflect the ideas of the contributors, many of whom have spent their careers attempting to resolve the biological functions of ADP-ribosylation.

This volume contains the proceedings of an International Symposium on "Second Messenger Systems - Molecular, Cellular and Behavioural Aspects", which was held at Tobago on June 16-17, 1994. The interaction of an extracellular agonist (First Messenger) with its plasma membrane receptor leads to the transmission of a signal across the cell membrane and results in the production and/or activation of other signalling molecules (Second Messengers). These Second Messengers control the action of many protein kinases and protein phosphatases and so lead to cellular responses. Although the biochemical basis of the transduction of signals in the main signalling systems in eukaryotic cells is probably largely known, intensified research is ongoing in the following areas: the discovery of specific substrates for many protein kinases; elucidation of the biological significance of the differential tissue expression and heterogeneity of many signalling proteins; and the unravelling of diverse interactions (such as signal potentiation, synergism, antagonism and neuronal co-transmission) between signalling systems.As knowledge from such studies accumulates, it is becoming clear that the "cross talk" interactions between signalling systems are important features of dynamic cell regulation. This volume is designed to summarize some aspects of the work on various Second Messenger Systems and the integration of signals with respect to plasma membrane receptors. Second Messenger generation and degradation, protein kinase and phosphatase, cell cycle control, and cellular learning and memory.

In vitro and animal studies show that vanadate and other Because most cellular components contain hydroxyl and/or vanadium compounds increase glucose transport activity and phosphate groups, vanadate reacts as shown in eq. 1, and 2 normalize glucose metabolism [1-5]. Furthermore, these with a variety of metabolites. For example, the reaction of insulin-mimetic compounds can be administered orally. Vana- vanadate with the 2'-hydroxyl group of the cofactor NAD date enhances the phosphoprotein formation which is attrib- generates an NADP analog, NADV (path b) [22]. NADV is uted to either the activation of protein kinases or inhibition an excellent cofactor for enzymes such as glucose-6-phos- of protein phosphatases. Despite the interest in document- phate dehydrogenase, 6-phosphogluconate dehydrogenase, ing the effects of vanadate on protein kinases, most reports and alcohol dehydrogenase [22]. The presence ofNADV have used indirect methods and studies with purified kinases could affect the levels of reducing equivalents in the cell, im- show weak, if any, interaction of vanadate with kinases as portant in maintaining a normal glucose metabolism.This a group of enzymes (reviewed in Refs. [6-8]). Vanadate type of mechanism is distinct from the vanadate-induced interacts potently with phosphatases and the inhibition is NADH oxidation by plasma membranes [23]. Organic attributed to a five-coordinate vanadate complex which vanadates have been shown to substitute for organic phos- mimics the transition state of the phosphate ester hydroly- phates in many of the enzymes related to glucose metabolism sis reaction (reviewed in Refs. [7,9]).

Diverse and distinct auto-, para-, and endocrine stimuli arriving at the surface of endothelium, smooth muscle cells, cardiomyocytes and fibroblasts within the myocardium, engage cell type-specific receptors, which lead to transmission of signals across the cell plasma membrane and result in the production and activation of second messengers. The most common mechanism by which these second messengers function is via direct or indirect activation of specific protein kinases. The current challenge for scientists is to identify the specific substrates (for example, metabolic enzymes, Ca2+-regulating proteins, transcription and mitotic factors) for the many protein kinases, to elucidate the biological significance of the cell type-specific expression heterogeneity of signalling proteins (eg membrane receptors, isoenzymes of protein kinase C, G-proteins) and to unravel the cross-talk interaction between the signalling systems (eg phospholipase C with adenylate cyclase and phospholipase C with phospholipase D).This text provides an up-to-date source of information for all scientists and clinicians interested in the mechanisms by which external signals are transmitted to the interior and regulation of a variety of physiological, pathological and pharmacological responses.

This issue of the serial contains original research papers as well as invited reviews dedicated to Professor Albert Wollenberger, founder of the Heart Research Group and for 21 years its head, on the occasion of the 40th anniversary of the inauguration of the Heart Research Group in Berlin-Buch, which today forms a part of the Max Delbruck Center for Molecular Medicine. The papers in this issue are written by researchers working in the field of cardiovascular research who together with Albert Wollenberger share the belief that an integrative application of advances in molecular and cellular biology will lead to new concepts for treatment and prevention of cardiovascular diseases.

This text contains original research papers as well as invited reviews, and is dedicated, on the occasion of the 40th anniversary of the inauguration of the Heart Research Group in Berlin-Buch that today forms a part of the Max Delbruck Center for Molecular Medicine, to Professor Albert Wollenberger, founder of the Heart Research Group and for 21 years its head. The papers in this issue are written by researchers working in the field of cardiovascular research who, together with Albert Wollenberger, share the belief that an integrative application of advances in molecular and cellular biology will lead to new concepts for treatment and prevention of cardiovascular diseases.

Experimental techniques are the life blood of science. The better the methodology is, the more reliable and accurate the results will be. Ultimately, this will lead to a clearer interpretation of those results and firmer conclusions from any set of experiments. Experimental methodology in the area of cardiovascular biochemistry and molecular biology has advanced considerably in the last decade. Because of these factors, it was thought that a focused issue of Molecular and Cellular Biochemistry dedicated to the novel, latest technological advances in the field was warranted. We must thank Dr Naranjan S. Dhalla, Editor-in-Chief of Molecular and Cellular Biochemistry, for his willingness to publish an issue with such a focus. We have attracted some of the leaders in the field of cardiovascular biology to submit articles describing some of the most novel, significant techniques currently in use in their laboratories. The purpose of the manuscripts was not to describe the recent experimental findings from each laboratory as is done in most conventional manuscripts. Instead, the purpose of the articles found within this focused volume of Molecular and Cellular Biochemistry was to describe how the technique is performed on the laboratory bench so that others less familiar with the technique may be able to use it in their own labs. The subjects described in this volume can be generally subdivided into three categories: molecular biology, cell biology and basic biochemistry. The methods cover wide areas including various DNA and RNA expression technologies, transfection techniques, quantification of ion flux movement, measurements of lipid metabolism, advances in the culture of specific cardiovascular cell populations, and the use of confocal microscopy to examine cell structure and function. We thank all of the authors who have contributed so much of their time and efforts and, most importantly, shared the `secrets' of these valuable techniques with the rest of the cardiovascular research community.

Since the 1980s, chemical and cellular studies have contributed enormously to our understanding of metal-induced carcinogenesis, and many hypotheses on the role of metals in pathophysiological processes have been investigated. The conference on "Molecular Mechanisms of Metal Toxicity and Carcinogenesis" in September 2000 focused on the latest research in molecular mechanisms of metal-induced toxicity and carcinogenesis. It promoted a multidisciplinary investigative approach and included presentations from international experts in this field.

Signalm transduction through phosphorylation and dephosphorylation of proteins in the cell is a well-recognized mechanism involved in countless physiological and pathological processes. Consequently, the enzymes, known as protein kinases, which catalyze the phosphorylation of proteins, are critical regulators of cellular events. One of these protein kinases is the protein kinase CK2 (also known as casein kinase 2) that has been implicated in multiple functions including control of cell growth and proliferation. CK2 is a protein serine/threonine kinase which is a highly conserved and ubiquitous protein kinase. It is localized in the cytoplasmic and nuclear compartments, which accords with its multiple functional activities in the cell. Pertinent to this is also the recognition that a large number of putative substrates for this kinase have been identified in various compartments of the cell. New evidence from several laboratories has further reinforced the involvement of CK2 in signal transduction related to many cellular functions, thus underscoring the significance of its functional role in normal and abnormal cell growth and proliferation.This volume provides an overview of the state of knowledge concerning the protein kinase. It brings together contributions from leading investigators engaged in research in this field. Key developments pertain to the elaboration of the crystal structure and definition of novel functions of the kinase, such as its role as an inhibitor of apoptosis. Additionally, the shuttling of the kinase to various compartments in response to physiological and stress stimuli appears to be a key feature of the functional regulation of its activity in the cell.

Guanylate cyclase research occupies a position of prominence in the study of signal transduction. Guanylate cyclase has several intriguing features, including existence in two major forms, membrane and soluble, each independently regulated by distinct mechanisms. The membrane form gives rise to a signal transduction story important to both peptide hormones and sensory neurons. This volume covers the evolution of the field, peptide hormone receptor work, membrane guanylate cycles, related retinal diseases, and the biochemistry and physiology of the soluble form. The 16 chapters are written by leaders in the field.

The special issue of "Molecular and Cellular Biochemistry" focuses on "Control of Gene Expression by Catecholamines and the Renin-Angiotensin System" in health and disease. In the 1990s great progress was made in the understanding of catecholamine- and angiotensin II-modulated gene expression. There is also increasing evidence that catecholamine and angiotensin II induced cellular injury arises not solely from classical pathways, but also from a perturbed gene expression. Taking into account that catecholamines and angiotensin II are vital for a balanced gene expression of many cells, the intriguing possibility arises that various disease are initiated or aggravated by such an imbalance. Catecholamine and angiotensin II influences can be in excess arising from, for example, hypercaloric food intake or psychosocial stress. During early progression of heart failure, sympathetic activity and angiotensin II influences also become increased. Due to beta-adrenergic receptor downregulation, depressed catecholamine influences are expected in the final stage of heart failure.An imbalanced influence of catecholamines and angiotensin II on gene expression leads to disordered molecular structures of the cell and an impaired cell function. This focused issue is organized into chapters concentrating on catecholamines, angiotensin II, and the interaction between catecholamines and angiotensin II. Basic biochemical processes are covered in detail and the potential of these pathways for explaining chronic diseases associated with excess catecholamine and angiotensin II influences should become apparent. It is hoped that this focused issue will trigger novel research into the development of drugs that are targeted at diseases characterized by an imbalanced gene expression involving catecholamines and angiotensin II.

This special issue contains research papers as well as invited reviews focused in the field of cardiac metabolism and its regulation under normal and disease conditions. These papers cover many areas under intensive and rapid development such as the regulation of fatty acid oxidation in the heart, the role of cardiac glycogen during ischemia, the role of CPT I isoenzymes, the pathophysiology of diabetic cardiomyopathy, cardiac protection through regulation of energy production, the role of fatty acid binding protein under normal and pathological conditions, and several other important topics in this area of research. This special issue in the "Developments in Molecular and Cellular Biochemistry" provides an up-to-date source of information for scientists and clinicians interested in the mechanism by which cardiac metabolism is regulated in health and disease and the mechanistic relationship between disturbances in cardiac metabolism and the genesis of cardiovascular diseases.

In 1996 the 75th anniversary of the discovery of insulin was celebrated at the University of Toronto, the scene of that discovery in 1921. This volume was stimulated by the scientific program which was staged at that time and brought together much of the world's best talent to discuss and analyze the most recent developments in our understanding of pancreatic function, insulin secretion, the interaction of insulin with its target tissues, the mechanism of insulin action at the cellular level, and the defects which underlie both Type I (insulin-dependent diabetes mellitus, IDDM) and Type II (noninsulin-dependent diabetes mellitus, NIDDM) forms of the disease. We have chosen to focus the present volume on work related to insulin action.

This text describes the use of quantitative methods in studies in organized metabolic systems, such as mathematical modelling and metabolic control analysis, for investigation of the problems of bioenergetics of the cell. It also presents experimental results. The following central problems of cellular bioenergetics are the focus of the discussions: the mechanisms of regulation of oxidative phosphorylation in cells "in vivo" in health and disease, the influence of fine intracellular structural organization on mitochondrial function, the intracellular networks of energy transfer and metabolic feedback signalling, the role of mitochondria in intracellular calcium cycling, and changes in mitochondrial membrane systems and cellular energetics under pathological conditions. Systematic studies from many laboratories presented in this volume show that many mitochondrial properties, including affinities for mitochondrial creatine kinase and its molecular biology are related to its molecular physiology and functional coupling to adenine nucleotide translocase, as well as its participation, together with the adenylate kinase system, in intracellular energy transfer.The results of the studies of creatine kinase-deficient transgenic mice are summarized and analyzed using mathematical models of the compartmentalized energy transfer, thus combining two research methods. All these results, together with physiological and NMR data on the cardiac metabolic and mitochondrial responses to workload changes, confirm the concept of metabolic networks of energy transfer and feedback regulation. The papers, mostly review articles, are written by experts in the field who analyze their experience of research and give insights into the future development of this increasingly important area of biological science.

The papers ofthis Special Issue of Molecular and Cellular Nutraceuticals are also known as 'health foods' but they also Biochemistry are invited, peer-reviewed submissions from include any product derived from animal or plant sources speakers who attended the 2nd World Conference of the which ultimately can provide a medical benefit. F our symposia International Society for MolecuIar Nutrition & Therapy. This on various aspects concerning nutraceutical products and the Conference was held fromAugust 2--4th, 1997 in Winnipeg, marketing ofthese compounds was addressed. It is hoped that Canada. The goal of the Conference was to advance our these interactions represent the start of a new, highly interesting knowledge concerning the molecular events which link scientific venture uniting the nutraceutical industry with the nutrition to various disease processes in the body. Attending main stream academic medical research community. The the meeting were scientists from 18 countries ineluding nutraceutical industry is expected to be a multibillion dollar Canada, the United States, Japan, the United Kingdom, a year business world-wide by the turn of the century.The Franee, the Czeeh Republie, Germany, the Netherlands, identification of the active ingredients in any number of Bahrain, Hong Kong, India, Israel, China, Kuwait,Argentina, health foods reputed to be medieally beneficial would be just Sweden, Australia and Mexieo. There were 56 Distinguished one of the goals of such a scientific interaction.

The articles collected in this volume largely arose from two related meetings held last spring. The first was held in Buenos Aires, Argentina on April 11-12, 1997 and was titled Nuevos Avances en el Fenomeno de Isquemia y Reperfusion (New Advances in the Phenomenon of Ischemia and Reperfusion). The second meeting took place in Stara Lesna located in the High Tatras Mountains of the Slovak Republic on June 27-30, 1997. Both meetings were sponsored by several organizations including the International Society and Federation of Cardiology, the International Society for Heart Research and The American Heart Association.

It is now generally recognized that protein kinase signalling is involved in virtually every aspect of cell function, including growth and proliferation. The field of protein phosphorylation, including the enzymes involved in this post-translational modification, continues to advance. Since the first international meeting on this topic, held in Heidelberg in 1994, several new avenues of CK2 research have emerged despite persistent deficiencies in our understanding of the regulation of its activity. Among the significant new directions are studies related to the structure of the enzyme, especially its crystal structure, as well as an interesting aspect of CK2 function that involves its subunits as binding partners of several other proteins. In addition, new data have been gathered on the role of CK2 in transcription as well as in certain other cellular functions. To address these various aspects of the progress of CK2, a number of key scientists from different parts of the world came together at the second international meeting on "A Molecular and Cellular View of Protein Kinase CK2", held at Villard de Lans near Grenoble on September 24-26, 1997.The meeting was attended by nearly 50 participants and included 28 presentations, which provide a view of the latest progress on protein kinase CK2.

The breadth of modern biology is characterized by a comprehension of phenomena at many levels of organization. Such levels of understanding range from the organismal to the molecular. It is when all these levels can be discussed together that a sense of true achievement begins to be felt. The topical area of fatty acid transport and metabolism was the focus of the Third International Conference on Lipid-Binding Proteins held at the University of Minnesota in May 1997. This volume contains a sampling of the proceedings of this meeting.

This special issue of Molecular and Cellular Biochemistry contains twenty-two selected research papers and reviews from a total of one hundred and ten presentations given at the 12th International Symposium on ADP-ribosylation Reactions: From Bacterial Pathogenesis to Cancer, held in Cancun, Mexico, May 10-14, 1997. The Symposium was hosted by the Sociedad Mexicana de Bioquimica and was sponsored by the University of North Texas Health Science Center, Fort Worth, TX, USA. This volume provides a state-of-the-art source of information for basic scientists and clinicians who are interested in the molecular, biochemical, and cellular aspects of protein-(ADP-ribose) transfer reactions in human health and disease.

The papers in this issue were contributed by close friends, the publication of this issue possible. Owing to some un- coworkers and pupils ofProfessor Setsuro Ebashi. They are expected troubles ofone ofthe editors (M. E. ) the publication dedicated to him to commemorate his great and pioneering ofthis issue has been greatly delayed, for which he sincerely contribution to the advancement of muscle physiology and apologizes to all the contributors and other editors. We biochemistry, which in course of time exerted a great in- believe that this issue reveals the present stateofresearch on fluence on the whole field oflife science. We would like to muscle and/or calcium that had been opened up by Professor express our cordial thanks to an the contributors who made Ebashi. Shoichi Imai, Niigata, Japan Makoto Endo, Saitama, Japan Iwao Ohtsuki, Fakuoka, Japan Molecular and Cellular Biochemistry 190: 3-4, 1999. Dedication Setsuro Ebashi was born in Tokyo on 31st August, 1922. There is aJapanese saying that 'Sandalwood is fragrant even in seed leaf. ' Genius displays itself even in childhood.Finishing the six-year course ofprimary school in five years and the five-year course ofmiddle school in four years, he entered the First High School, the most prestigious high school in Japan, at the age ofonly 15. In July 1942, when he was an undergraduate student of FacultyofMedicine,Tokyo Imperial University (now called University ofTokyo), he by chance visited the laboratory of Dr.

Stress reaction is likely to play a crucial role in a variety of degenerative diseases including cancer and cardiovascular diseases. The process of stress adaptation may appear to be simple, but in reality this is a very complex process and we are only beginning to understand the mechanism of adaptation. In January, 1998, scientists from around the world assembled to discuss the potential applicability of the concept of stress adaptation in the clinical arena. This volume contains original research papers presented on this subject during the conference Stress Adaptation, Prophylaxis and Treatment held in Calcutta, India, and serves as an up-to-date source of information for scientists, as well as clinicians interested in applying the concept of stress adaptation to the cure of diseases.

In October 1995, the 1st Colloquium on Mitochondria and Myopathies in Halle/Saale was organized in Halle/Saale by the editors of this focused issue. The meeting took up what might be called an East German tradition: from 1976 to 1990 Andreas Schmidt organized seven clinically orientated Colloquia on Myology in Jena, and from 1974 to 1990 a series of twelve Colloquia on Mitochondria focused on basic research aspects was arranged by Wolfgang Kunz in Magdeburg. At those meetings, East Germany was a mediator between East European, West European and American scientists. In continuation of this tradition, scientists from more than 17 countries working on mitochondria as neurologists, biochemists, geneticists, or as physiologists came to Halle. The title of the colloquium indicated the combination of both basic and clinical mitochondrial research. The most important contributions of this meeting are now published in this focused issue. We thank all authors for their patience and cooperation that have made it possible to produce this unique collection of papers representing current knowledge on detection of mitochondrial causes of diseases. We especially thank Prof. N.S. Dhalla for making it possible to publish these contributions together in this focused issue and also as a hard-cover book.