T16G12.6/IMPORTIN 13-mediated cytoplasm-to-nucleus transport of the THAP transcription factor LIN-15B controls autophagy and lysosome function in <i>C. elegans</i>

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 <i>C. elegans</i> development remain unknown. Here we showed that the THAP domain-containing transcription factor LIN-15B modulates autophagy activity during <i>C. elegans</i> development. Loss of function of <i>lin-15B</i> 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 <i>lin-15B</i> 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 <i>C. elegans</i>.<b>Abbreviations:</b> 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.