Identification of modulators of the mitochondrial stress response in Caenorhabditis elegans:
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| Format: | Abschlussarbeit Buch |
| Sprache: | English |
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2013
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| Online-Zugang: | Inhaltsverzeichnis |
| Beschreibung: | 127 S. Ill., graph. Darst. 30 cm |
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| adam_text | IMAGE 1
TABLE OF CONTENTS
1 SUMMARY 1
2 INTRODUCTION 3
2.1 COMPARTMENT-SPECIFIC STRESS RESPONSES 5
2.1.1 THE CYTOSOL . 6
2.1.2 THE ENDOPLASMATIC RETICULUM 8
2.1.3 THE MITOCHONDRIA 9
2.2 THE GENERATION OF ROS AT THE MITOCHONDRIA 12
2.3 CELLULAR SURVEILLANCE ACTIVATED DEFENSES 14
3 RESULTS 15
3.1 MITOCHONDRIAL ROS INDUCES THE UPR ML 17
3.1.1 PARAQUAT ACTIVATES THE EXPRESSION OF NUCLEAR-ENCODED MITOCHONDRIAL
CHAPERONES 17
3.1.2 THE TRANSCRIPTION OF NON-MITOCHONDRIAL HSP70 CHAPERONES IS NOT
INDUCED BY PARAQUAT.. 23
3.1.3 SEVERAL MITOCHONDRIAL ROS GENERATORS ACTIVATE HSP-6 REPORTER
EXPRESSION 25
3.1.4 THE ROS SCAVENGER NAC REDUCES PARAQUAT-MEDIATED HSP-6 INDUCTION 27
3.1.5 NON-MITOCHONDRIAL STRESS DOES NOT INDUCE HSP-6 28
3.1.6 PARAQUAT TREATMENT ALTERS MITOCHONDRIAL MORPHOLOGY 29
3.1.7 PARAQUAT-INDUCED UPR MT REQUIRES ATFS-1, BUT IS INDEPENDENT OF
HAF-1 30
3.2 THE EFFECT OF PARAQUAT ON OTHER STRESS RESPONSES 32
3.2.1 PARAQUAT DOES NOT INDUCE THE UPR OF THE ER OR THE CYTOSOL 32
3.2.2 PARAQUAT-INDUCED UPR MI IS INDEPENDENT OF KEY REGULATORS OF OTHER
CELLULAR STRESS
RESPONSES 35
3.2.3 PARAQUAT ACTIVATES THE PHASE II DETOXIFICATION RESPONSE DEPENDENT
ON SKN-1/NRF2 37
3.3 GENOME-SCALED RNAI SCREENING IDENTIFIES 55 GENES REQUIRED FOR
PARAQUAT-INDUCED UPR MT .... 39
HTTP://D-NB.INFO/1042072094
IMAGE 2
3.3.1 PRODUCTS OF THE SCREENING POSITIVES ARE INVOLVED IN SEVERAL
BIOLOGICAL FUNCTIONS 39
3.3.2 ATFS-1,PIFK-1 AND RPL-36 ARE REQUIRED FOR ISP-1 (QMLSO)-INDUCED
UPR MT 43
3.3.3 KNOCKDOWN OF ATFS-1,PTFK-1 AND RPL-36 INCREASES PARAQUAT
SENSITIVITY 44
3.3.4 A REDUCED TRANSLATION DOES NOT SUFFICE TO PHENOCOPY RNAI WITH
RIBOSOMAL SUBUNITS 45
3.4 MOST SCREENING POSITIVES SELECTIVELY AFFECT THE RESPONSE TO
MITOCHONDRIAL STRESS 47
3.4.1 THE PHASE II DETOXIFICATION RESPONSE 47
3.4.2 THE CYTOSOLIC UPR 49
3.4.3 THE ^-INDUCED UPR MT 50
3.4.4 THE UPR ER 52
3.5 SURVEILLANCE-ACTIVATED DEFENSES SUPPRESS PARAQUAT-INDUCED UPR* 53
3.5.1 CSADDS-ACTIVATING RNAIS CAUSE MORE SEVERE DETRIMENT THAN 0.5 MM
PARAQUAT 53
3.5.2 LOSS OF KGB-1 SUPPRESSES UPR MT INHIBITION BY ELT-2 AND RPL-36
RNAI 57
3.5.3 LOSS OF KGB-1 DOES NOT SUPPRESS UPR MT INHIBITION BY ATFS-1 AND
PIFK-1 RNAI 58
4 DISCUSSION 63
4.1 PARAQUAT ACTIVATES ATFS-1 INDEPENDENT OF HAF-1 65
4.2 CELLULAR SURVEILLANCE ACTIVATED DEFENSES CROSSTALK WITH THE UPR MT
68
4.3 ATFS-1 ACTIVATES THE PHASE II DETOXIFICATION RESPONSE FOLLOWING
PARAQUAT TREATMENT 73
4.4 PIFK-1 IS REQUIRED FOR BOTH UPR AND UPR ER 75
4.5 THE CONSEQUENCES OF MITOCHONDRIAL STRESS 77
5 MATERIAL AND METHODS 79
5.1 MATERIAL 81
5.1.1 C. ELEGANS STRAINS 81
5.1.2 BACTERIA STRAINS 82
5.1.3 OLIGONUCLEOTIDES 82
5.1.4 BUFFERS AND SOLUTIONS 82
5.1.5 CHEMICAL COMPOUNDS 83
IMAGE 3
5.1.6 SOFTWARE 83
5.1.7 EQUIPMENT 83
5.2 METHODS 85
5.2.1 MAINTENANCE OF C. ELEGANS 85
5.2.2 DECONTAMINATION OF C. ELEGANS 85
5.2.3 SYNCHRONIZATION OF C. ELEGANS POPULATIONS 85
5.2.4 RNA INTERFERENCE ASSAYS 86
5.2.5 CROSSES 87
5.2.6 BACKCROSSES 87
5.2.7 GENOTYPING 89
5.2.8 DNA SEQUENCING 90
5.2.9 STRESS ASSAYS 90
5.2.10 NAC ASSAY 91
5.2.11 PARAQUAT RESISTANCE TEST 91
5.2.12 FOOD AVERSION ASSAY 91
5.2.13 STAINING OF MITOCHONDRIA 92
5.2.14 AUTOPHAGY ASSAY 93
5.2.15 INTEGRATION OF TRANSGENES 93
5.2.16 QUANTITATIVE REAL TIME POLYMERASE CHAIN REACTION 93
5.2.17 MICROSCOPY 95
5.2.18 IMAGE ANALYSIS 95
5.2.19 STATISTICAL ANALYSIS 96
5.2.20 BIOINFORMATICS 97
6 REFERENCES 99
7 DANKSAGUNG 115
8 APPENDIX 117
IMAGE 4
8.1 OVERLAP OF THE SCREEN PERFORMED IN THIS STUDY WITH THE AVERSION
SCREEN PERFORMED BY MELO
AND RUVKUN, 2012 [123] 119
8.2 ABBREVIATIONS 121
8.3 LIST OF FIGURES 123
8.2 LIST OF TABLES 127
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| author | Runkel, Eva Diana |
| author_GND | (DE-588)1041837631 |
| author_facet | Runkel, Eva Diana |
| author_role | aut |
| author_sort | Runkel, Eva Diana |
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| building | Verbundindex |
| bvnumber | BV041296741 |
| ctrlnum | (OCoLC)861226904 (DE-599)DNB1042072094 |
| dewey-full | 571.6571257 |
| dewey-hundreds | 500 - Natural sciences and mathematics |
| dewey-ones | 571 - Physiology & related subjects |
| dewey-raw | 571.6571257 |
| dewey-search | 571.6571257 |
| dewey-sort | 3571.6571257 |
| dewey-tens | 570 - Biology |
| discipline | Biologie |
| format | Thesis Book |
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| indexdate | 2024-07-10T00:53:38Z |
| institution | BVB |
| language | English |
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| spelling | Runkel, Eva Diana Verfasser (DE-588)1041837631 aut Identification of modulators of the mitochondrial stress response in Caenorhabditis elegans vorgelegt von Eva Diana Runkel 2013 127 S. Ill., graph. Darst. 30 cm txt rdacontent n rdamedia nc rdacarrier Freiburg (Breisgau), Univ., Diss., 2013 (DE-588)4113937-9 Hochschulschrift gnd-content DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=026745611&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Runkel, Eva Diana Identification of modulators of the mitochondrial stress response in Caenorhabditis elegans |
| subject_GND | (DE-588)4113937-9 |
| title | Identification of modulators of the mitochondrial stress response in Caenorhabditis elegans |
| title_auth | Identification of modulators of the mitochondrial stress response in Caenorhabditis elegans |
| title_exact_search | Identification of modulators of the mitochondrial stress response in Caenorhabditis elegans |
| title_full | Identification of modulators of the mitochondrial stress response in Caenorhabditis elegans vorgelegt von Eva Diana Runkel |
| title_fullStr | Identification of modulators of the mitochondrial stress response in Caenorhabditis elegans vorgelegt von Eva Diana Runkel |
| title_full_unstemmed | Identification of modulators of the mitochondrial stress response in Caenorhabditis elegans vorgelegt von Eva Diana Runkel |
| title_short | Identification of modulators of the mitochondrial stress response in Caenorhabditis elegans |
| title_sort | identification of modulators of the mitochondrial stress response in caenorhabditis elegans |
| topic_facet | Hochschulschrift |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=026745611&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
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