Mitochondrial SSBP1 protects cells from proteotoxic stresses by potentiating stress-induced HSF1 transcriptional activity

• Published in: Nature communications Vol. 6; no. 1; p. 6580
• Main Authors: Tan, Ke, Fujimoto, Mitsuaki, Takii, Ryosuke, Takaki, Eiichi, Hayashida, Naoki, Nakai, Akira
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12.03.2015; Nature Publishing Group; Nature Pub. Group
• Subjects: 13; 13/109; 13/51; 13/89; 14/19; 38/15; 38/23; 38/61; 631/337/572; 631/80/389; 631/80/470/1981; 631/80/86/2366; Active Transport, Cell Nucleus; Amino Acid Sequence; Animals; Cell Nucleus - metabolism; Cell Survival; Chromatin - chemistry; Chromatin - metabolism; Cytoplasm - metabolism; DNA Helicases - metabolism; DNA, Mitochondrial - metabolism; DNA-Binding Proteins - metabolism; Heat Shock Transcription Factors; HEK293 Cells; HeLa Cells; HSP70 Heat-Shock Proteins - metabolism; Humanities and Social Sciences; Humans; Membrane Potential, Mitochondrial; Mice; Mitochondria - metabolism; Mitochondrial DNA; Mitochondrial Proteins - metabolism; Molecular Sequence Data; multidisciplinary; Nuclear Proteins - metabolism; Protein Binding; Protein Structure, Tertiary; Protein Transport; Science; Science (multidisciplinary); Sequence Homology, Amino Acid; Temperature; Transcription Factors - metabolism; Transcription, Genetic; Translocation
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms7580

Heat-shock response is an adaptive response to proteotoxic stresses including heat shock, and is regulated by heat-shock factor 1 (HSF1) in mammals. Proteotoxic stresses challenge all subcellular compartments including the mitochondria. Therefore, there must be close connections between mitochondrial signals and the activity of HSF1. Here, we show that heat shock triggers nuclear translocation of mitochondrial SSBP1, which is involved in replication of mitochondrial DNA, in a manner dependent on the mitochondrial permeability transition pore ANT–VDAC1 complex and direct interaction with HSF1. HSF1 recruits SSBP1 to the promoters of genes encoding cytoplasmic/nuclear and mitochondrial chaperones. HSF1–SSBP1 complex then enhances their induction by facilitating the recruitment of a chromatin-remodelling factor BRG1, and supports cell survival and the maintenance of mitochondrial membrane potential against proteotoxic stresses. These results suggest that the nuclear translocation of mitochondrial SSBP1 is required for the regulation of cytoplasmic/nuclear and mitochondrial proteostasis against proteotoxic stresses. Heat shock induces proteotoxic stress, and the cellular response is mediated by heat-shock factor 1 (HSF1). Here, Tan et al. show that following heat shock, mitochondrial SSBP1 translocates to the nucleus and binds HSF1 to enhance the expression of chaperones and support the maintenance of mitochondrial function.