Mitochondrial enzymes are protected from stress-induced aggregation by mitochondrial chaperones and the Pim1/LON protease
| Autor: | Catherina Baitzel, Wolfgang Voos, Tom Bender, Ilka Lewrenz, Sebastian Franken |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Proteases
Saccharomyces cerevisiae Proteins Biosynthesis and Biodegradation Saccharomyces cerevisiae Mitochondrion Protein aggregation Mitochondrial Proteins Protein structure ATP-Dependent Proteases Stress Physiological HSP70 Heat-Shock Proteins Heat shock Protein Structure Quaternary Molecular Biology biology Serine Endopeptidases Cell Biology Chaperonin 60 Articles Cell biology Hsp70 Mitochondria Enzyme Activation Kinetics Oxidative Stress Biochemistry Chaperone (protein) biology.protein HSP60 Reactive Oxygen Species Heat-Shock Response Molecular Chaperones |
| Zdroj: | Molecular Biology of the Cell |
| ISSN: | 1939-4586 |
| Popis: | Protein aggregation negatively affects key enzymes of major metabolic pathways in mitochondria. The main mitochondrial chaperones Hsp70 and Hsp60 have a limited protective effect against aggregation. In contrast, the ATP-dependent matrix protease Pim1/LON significantly reduces aggregate levels by preventing the accumulation of damaged polypeptides. Proteins in a natural environment are constantly challenged by stress conditions, causing their destabilization, unfolding, and, ultimately, aggregation. Protein aggregation has been associated with a wide variety of pathological conditions, especially neurodegenerative disorders, stressing the importance of adequate cellular protein quality control measures to counteract aggregate formation. To secure protein homeostasis, mitochondria contain an elaborate protein quality control system, consisting of chaperones and ATP-dependent proteases. To determine the effects of protein aggregation on the functional integrity of mitochondria, we set out to identify aggregation-prone endogenous mitochondrial proteins. We could show that major metabolic pathways in mitochondria were affected by the aggregation of key enzyme components, which were largely inactivated after heat stress. Furthermore, treatment with elevated levels of reactive oxygen species strongly influenced the aggregation behavior, in particular in combination with elevated temperatures. Using specific chaperone mutant strains, we showed a protective effect of the mitochondrial Hsp70 and Hsp60 chaperone systems. Moreover, accumulation of aggregated polypeptides was strongly decreased by the AAA-protease Pim1/LON. We therefore propose that the proteolytic breakdown of aggregation-prone polypeptides represents a major protective strategy to prevent the in vivo formation of aggregates in mitochondria. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|