HSB-1/HSF-1 pathway modulates histone H4 in mitochondria to control mtDNA transcription and longevity

作者/單位: 許翺麟/老化醫學博士學位學程
期刊名稱: SCIENCE ADVANCES
IF值: 13.117
領域排名: MULTIDISCIPLINARY SCIENCES  (4/71)  5.6%
文章摘要: 

Heat shock factor-1 (HSF-1) is a master regulator of stress responses across taxa. Overexpression of HSF-1 or genetic ablation of its conserved negative regulator, heat shock factor binding protein 1 (HSB-1), results in robust life-span extension in Caenorhabditis elegans Here, we found that increased HSF-1 activity elevates histone H4 levels in somatic tissues during development, while knockdown of H4 completely suppresses HSF-1-mediated longevity. Moreover, overexpression of H4 is sufficient to extend life span. Ablation of HSB-1 induces an H4-dependent increase in micrococcal nuclease protection of both nuclear chromatin and mitochondrial DNA (mtDNA), which consequently results in reduced transcription of mtDNA-encoded complex IV genes, decreased respiratory capacity, and a mitochondrial unfolded protein response-dependent life-span extension. Collectively, our findings reveal a previously unknown role of HSB-1/HSF-1 signaling in modulation of mitochondrial function via mediating histone H4-dependent regulation of mtDNA gene expression and concomitantly acting as a determinant of organismal longevity.

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發表者簡介


單位:醫學院老化醫學博士學位學程教授

研究專長:

  • 老化生物學
  • 分子遺傳學
  • 生物化學

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