C. elegansの発生においてオートファジーを制御するLIN-15Bの役割を発見(LIN-15B Unveiled as Key Transcriptional Repressor Regulating Autophagy in C. elegans Development)

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2025-04-10 中国科学院(CAS)

C. elegansの発生においてオートファジーを制御するLIN-15Bの役割を発見(LIN-15B Unveiled as Key Transcriptional Repressor Regulating Autophagy in C. elegans Development)
Model showing that IPO-13-mediated cytoplasm-to-nucleus transport of LIN-15B controls autophagy activity. (Image by ZHANG Hong’s group)

中国科学院生物物理研究所のZHANG Hong教授らの研究チームは、『Autophagy』誌にて、線虫(C. elegans)における新たなオートファジー制御機構を発見した。研究では、転写因子LIN-15BがIMPORTIN-13(IPO-13)により核へ輸送され、オートファジー関連遺伝子の転写を抑制する役割を果たすことが明らかになった。IPO-13欠損や飢餓条件下ではLIN-15Bが核内に移行できず、オートファジー関連遺伝子の発現が上昇、オートファジーフラックスが増加する。LIN-15BはTHAPドメインを持ち、クロマチン修飾や染色体分配にも関与する。本研究は、栄養状態に応じたオートファジー制御の新たな分子機構を提示するものである。

<関連情報>

線虫におけるTHAP転写因子LIN-15BのT16G12.6/IMPORTIN 13を介した細胞質から核への輸送はオートファジーとリソソーム機能を制御する T16G12.6/IMPORTIN 13-mediated cytoplasm-to-nucleus transport of the THAP transcription factor LIN-15B controls autophagy and lysosome function in C. elegans

Xiaoli Ma,Xiaomeng Gou & Hong Zhang
Autophagy  Published:02 Apr 2025
DOI:https://doi.org/10.1080/15548627.2025.2482724

ABSTRACT

Transcriptional regulation of genes involved in the macroautophagy/autophagy-lysosome pathway acts as an important mechanism for controlling autophagy activity. The factors that globally regulate autophagy activity at the transcriptional level during C. elegans development remain unknown. Here we showed that the THAP domain-containing transcription factor LIN-15B modulates autophagy activity during C. elegans development. Loss of function of lin-15B suppresses the autophagy defect caused by impaired autophagosome maturation and promotes lysosome biogenesis and function. LIN-15B maintains the repressed state of genes involved in the autophagy pathway. Accordingly, loss of function of lin-15B upregulates a plethora of genes involved in autophagosome formation and maturation as well as lysosome biogenesis and function. The cytoplasm-to-nucleus translocation of LIN-15B is mediated by the T16G12.6/IMPORTIN 13/IPO-13 receptor and modulated by nutrient status. Our study uncovers that LIN-15B integrates environmental cues into transcriptional control of a network of genes involved in autophagy in C. elegans.

Abbreviations: ATG: autophagy related; DIC: differential interference contrast; EPG: ectopic PGL granules; ER: endoplasmic reticulum; FOXO: forkhead box O; GFP: green fluorescent protein; SQST-1: SeQueSTosome related 1; SynMuv: synthetic multivulva; IPO-13: importin 13; TFEB: transcription factor EB.

生物工学一般
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