Funkční charakterizace LACE1 ATPázy a mitochondriálních AAA proteáz YME1L a AFG3L2 v mitochondriální proteinové homeostáze.
| Autor: | Tesařová, Jana |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
proteáza YME1L
Key words: AFG3L2 protease p53 tumor suppressor protein komplex IV respiratory chain apoptosis translokace complex IV proteáza AFG3L2 Klíčová slova: apoptóza mitochondrie oxidativní fosforylace YME1L protease translocation LACE1 protein mitochondria protein LACE1 tumor-supresorový protein p53 oxidative phosphorylation dýchací řetězec |
| Druh dokumentu: | Doctoral Thesis |
| Popis: | Mitochondrial protein homeostasis is crucial for cellular function and integrity. It is ensured by many specific mitochondrial proteases with possible chaperone functions located across the various mitochondrial subcompartments. In the first part, we have focused on characterization of functional overlap and cooperativity of proteolytic subunits AFG3L2 and YME1L of the mitochondrial inner membrane complexes m- and i-AAA in HEK293 cells. The double AFG3L2/YME1L knockdown cells showed severe alteration in OPA1 protein processing, marked elevation in OMA1 protease and severe reduction in SPG7. Our results reveal cooperative and partly redundant involvement of AFG3L2 and YME1L in the maintenance of mitochondrial protein homeostasis and further emphasize their importance for mitochondrial and cellular function and integrity. The aim of the second part was to characterize the cellular function of LACE1 (lactation elevated 1) in mitochondrial protein homeostasis. LACE1 protein is a human homologue of yeast Afg1 (ATPase family gene 1) ATPase. We show that LACE1 is a mitochondrial integral membrane protein that exists as a part of three complexes of approximately 140, 400 and 500 kDa. We demonstrate that LACE1 mediates degradation of nuclear-encoded complex IV subunits COX4, COX5A and COX6A. Using affinity... |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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