Increased levels of mitochondrial import factor Mia40 prevent the aggregation of polyQ proteins in the cytosol

ABSTRACT: The formation of protein aggregates is a hallmark of neurodegenerative diseases. Observations on patient samples and model systems demonstrated links between aggregate formation and declining mitochondrial functionality, but causalities remain unclear. We used Saccharomyces cerevisiae to analyze how mitochondrial processes regulate the behavior of aggregation-prone polyQ protein derived from human huntingtin. Expression of Q97-GFP rapidly led to insoluble cytosolic aggregates and cell death. Although aggregation impaired mitochondrial respiration only slightly, it considerably interfered with the import of mitochondrial precursor proteins. Mutants in the import component Mia40 were hypersensitive to Q97-GFP, whereas Mia40 overexpression strongly suppressed the formation of toxic Q97-GFP ag

SUBMITTER: Dr. Anna, M Schlagowski 

PROVIDER: S-SCDT-EMBOJ-2021-107913 | biostudies-other |

REPOSITORIES: biostudies-other