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The Intracellular Distribution of the Small GTPase Rho5 and Its Dimeric Guanidine Nucleotide Exchange Factor Dck1/Lmo1 Determine Their Function in Oxidative Stress Response
- Source :
- International Journal of Molecular Sciences; Volume 23; Issue 14; Pages: 7896
- Publication Year :
- 2022
-
Abstract
- Rho5, the yeast homolog of human Rac1, is a small GTPase which regulates the cell response to nutrient and oxidative stress by inducing mitophagy and apoptosis. It is activated by a dimeric GEF composed of the subunits Dck1 and Lmo1. Upon stress, all three proteins rapidly translocate from the cell surface (Rho5) and a diffuse cytosolic distribution (Dck1 and Lmo1) to mitochondria, with translocation of the GTPase depending on both GEF subunits. We here show that the latter associate with mitochondria independent from each other and from Rho5. The trapping of Dck1-GFP or GFP-Lmo1 to the mitochondrial surface by a specific nanobody fused to the transmembrane domain (TMD) of Fis1 results in a loss of function, mimicking the phenotypes of the respective gene deletions, dck1 or lmo1. Direct fusion of Rho5 to Fis1TMD, i.e., permanent attachment to the mitochondria, also mimics the phenotypes of an rho5 deletion. Together, these data suggest that the GTPase needs to be activated at the plasma membrane prior to its translocation in order to fulfill its function in the oxidative stress response. This notion is substantiated by the observation that strains carrying fusions of Rho5 to the cell wall integrity sensor Mid2, confining the GTPase to the plasma membrane, retained their function. We propose a model in which Rho5 activated at the plasma membrane represses the oxidative stress response under standard growth conditions. This repression is relieved upon its GEF-mediated translocation to mitochondria, thus triggering mitophagy and apoptosis.
- Subjects :
- rho GTP-Binding Proteins
Saccharomyces cerevisiae Proteins
Nucleotides
Organic Chemistry
General Medicine
Saccharomyces cerevisiae
Rho-type GTPase
mitochondria
oxidative stress
membrane trapping
LIM Domain Proteins
Catalysis
Computer Science Applications
Inorganic Chemistry
DNA-Binding Proteins
Mitochondrial Proteins
Oxidative Stress
Guanine Nucleotide Exchange Factors
Humans
Physical and Theoretical Chemistry
Molecular Biology
Spectroscopy
Guanidine
Monomeric GTP-Binding Proteins
Transcription Factors
Subjects
Details
- ISSN :
- 14220067
- Volume :
- 23
- Issue :
- 14
- Database :
- OpenAIRE
- Journal :
- International journal of molecular sciences
- Accession number :
- edsair.doi.dedup.....a8f11a2c7f3c66eca9f2faafad868f58