Crisis in Energy Metabolism – Mitochondrial Defects and a New Disease Entity

.........................................................................................................................5 LIST OF PUBLICATIONS .................................................................................................6 ABBREVIATIONS ..............................................................................................................8 CONTENTS..........................................................................................................................9 BACKGROUND.................................................................................................................11 CELLULAR ENERGY AND DISEASE .......................................................................................11 MITOCHONDRIA.................................................................................................................13 THE OXPHOS SYSTEM......................................................................................................13 MITOCHONDRIAL DISEASES................................................................................................15 INTRODUCTION AND AIMS..........................................................................................18 PAPER I AND II ..................................................................................................................18 PAPER III ..........................................................................................................................19 PAPER IV ..........................................................................................................................20 PAPER V............................................................................................................................21 RESULTS AND DISCUSSION .........................................................................................24 PAPER I .............................................................................................................................24 PAPER II............................................................................................................................25 PAPER III ..........................................................................................................................27 PAPER IV ..........................................................................................................................29 PAPER V............................................................................................................................32 GENERAL CONCLUSIONS AND MAJOR NEW FINDINGS ......................................35 MATERIALS AND METHODS........................................................................................37 PATIENTS ..........................................................................................................................37 MORPHOLOGICAL ANALYSES..............................................................................................37 BIOCHEMISTRY..................................................................................................................39 MOLECULAR GENETICS ......................................................................................................39 PROTEIN ANALYSES ...........................................................................................................42 WEB-SOURCES...................................................................................................................43 POPULÄRVETENSKAPLIG SAMMANFATTNING.....................................................44 ACKNOWLEDGEMENTS ...............................................................................................46 REFERENCES...................................................................................................................48