Fuko Horie, Ryoko Ando, Koharu Sekimoto, Vo Thi Anh Nguyet, Shingo Izawa
{"title":"酵母Hsp78通过轻度乙醇胁迫预处理在线粒体蛋白质量控制中对严重乙醇胁迫的适应中起重要作用。","authors":"Fuko Horie, Ryoko Ando, Koharu Sekimoto, Vo Thi Anh Nguyet, Shingo Izawa","doi":"10.1016/j.bbagen.2025.130804","DOIUrl":null,"url":null,"abstract":"<div><div>Severe ethanol stress (10 % v/v) causes the denaturation and aggregation of certain mitochondrial proteins, such as aconitase (Aco1), forming the deposits of unfolded mitochondrial proteins (DUMPs) in the budding yeast <em>Saccharomyces cerevisiae</em>. Pre-exposing yeast cells to mild stress often induces adaptation to subsequent severe stress. However, whether pre-exposing yeast cells to mild ethanol stress mitigates mitochondrial protein aggregation remains unclear. Therefore, in this study, we examined the effects of pre-exposing yeast cells to mild ethanol stress on the yeast mitochondrial protein quality control (mtPQC) system under severe ethanol stress. Pretreatment with 6 % (v/v) ethanol significantly mitigated the formation of DUMPs and Aco1 aggregates under subsequent 10 % ethanol stress in wild-type cells but not in <em>hsp78</em>∆ and <em>mdj1</em>∆ cells. Pretreatment with 6 % ethanol increased the protein levels of mtPQC-related factors, Hsp78, Mdj1, and Hsp10; however, <em>hsp78</em>∆ cells showed significantly lower levels of Ssc1 (mtHsp70) and its co-chaperone Mdj1 than wild-type cells. Moreover, intracellular reactive oxygen species levels and the frequency of respiration-deficient mutants under 10 % ethanol stress were reduced after pretreatment with 6 % ethanol in wild-type cells but not in <em>hsp78</em>∆ cells. Overall, this study demonstrated that pre-exposing yeast cells to mild ethanol stress mitigated ethanol-induced mitochondrial damage by activating the mtPQC system, including <em>HSP78</em> expression, providing novel insights into the effects of ethanol stress on mitochondria and the corresponding responses in yeast.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 6","pages":"Article 130804"},"PeriodicalIF":2.8000,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Yeast Hsp78 plays an essential role in adapting to severe ethanol stress via mild ethanol stress pretreatment in mitochondrial protein quality control\",\"authors\":\"Fuko Horie, Ryoko Ando, Koharu Sekimoto, Vo Thi Anh Nguyet, Shingo Izawa\",\"doi\":\"10.1016/j.bbagen.2025.130804\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Severe ethanol stress (10 % v/v) causes the denaturation and aggregation of certain mitochondrial proteins, such as aconitase (Aco1), forming the deposits of unfolded mitochondrial proteins (DUMPs) in the budding yeast <em>Saccharomyces cerevisiae</em>. Pre-exposing yeast cells to mild stress often induces adaptation to subsequent severe stress. However, whether pre-exposing yeast cells to mild ethanol stress mitigates mitochondrial protein aggregation remains unclear. Therefore, in this study, we examined the effects of pre-exposing yeast cells to mild ethanol stress on the yeast mitochondrial protein quality control (mtPQC) system under severe ethanol stress. Pretreatment with 6 % (v/v) ethanol significantly mitigated the formation of DUMPs and Aco1 aggregates under subsequent 10 % ethanol stress in wild-type cells but not in <em>hsp78</em>∆ and <em>mdj1</em>∆ cells. Pretreatment with 6 % ethanol increased the protein levels of mtPQC-related factors, Hsp78, Mdj1, and Hsp10; however, <em>hsp78</em>∆ cells showed significantly lower levels of Ssc1 (mtHsp70) and its co-chaperone Mdj1 than wild-type cells. Moreover, intracellular reactive oxygen species levels and the frequency of respiration-deficient mutants under 10 % ethanol stress were reduced after pretreatment with 6 % ethanol in wild-type cells but not in <em>hsp78</em>∆ cells. Overall, this study demonstrated that pre-exposing yeast cells to mild ethanol stress mitigated ethanol-induced mitochondrial damage by activating the mtPQC system, including <em>HSP78</em> expression, providing novel insights into the effects of ethanol stress on mitochondria and the corresponding responses in yeast.</div></div>\",\"PeriodicalId\":8800,\"journal\":{\"name\":\"Biochimica et biophysica acta. 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Yeast Hsp78 plays an essential role in adapting to severe ethanol stress via mild ethanol stress pretreatment in mitochondrial protein quality control
Severe ethanol stress (10 % v/v) causes the denaturation and aggregation of certain mitochondrial proteins, such as aconitase (Aco1), forming the deposits of unfolded mitochondrial proteins (DUMPs) in the budding yeast Saccharomyces cerevisiae. Pre-exposing yeast cells to mild stress often induces adaptation to subsequent severe stress. However, whether pre-exposing yeast cells to mild ethanol stress mitigates mitochondrial protein aggregation remains unclear. Therefore, in this study, we examined the effects of pre-exposing yeast cells to mild ethanol stress on the yeast mitochondrial protein quality control (mtPQC) system under severe ethanol stress. Pretreatment with 6 % (v/v) ethanol significantly mitigated the formation of DUMPs and Aco1 aggregates under subsequent 10 % ethanol stress in wild-type cells but not in hsp78∆ and mdj1∆ cells. Pretreatment with 6 % ethanol increased the protein levels of mtPQC-related factors, Hsp78, Mdj1, and Hsp10; however, hsp78∆ cells showed significantly lower levels of Ssc1 (mtHsp70) and its co-chaperone Mdj1 than wild-type cells. Moreover, intracellular reactive oxygen species levels and the frequency of respiration-deficient mutants under 10 % ethanol stress were reduced after pretreatment with 6 % ethanol in wild-type cells but not in hsp78∆ cells. Overall, this study demonstrated that pre-exposing yeast cells to mild ethanol stress mitigated ethanol-induced mitochondrial damage by activating the mtPQC system, including HSP78 expression, providing novel insights into the effects of ethanol stress on mitochondria and the corresponding responses in yeast.
期刊介绍:
BBA General Subjects accepts for submission either original, hypothesis-driven studies or reviews covering subjects in biochemistry and biophysics that are considered to have general interest for a wide audience. Manuscripts with interdisciplinary approaches are especially encouraged.