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<p>Autophagy is a fundamental cellular recycling process that maintains homeostasis during animal development and under nutrient-limiting conditions. In our previous work, we employed autophagy-dependent cell death (ADCD) in the obsolete <i>Drosophila</i> larval midgut as a model to identify the enzymes involved in protein modification via ubiquitination with potential roles in autophagy regulation. From a genetic screen we identified RING E3 ligase RCHY1 as a candidate regulator. Here, we demonstrate that RCHY1 is essential for autophagy regulation during larval midgut ADCD in <i>Drosophila</i> and promotes autophagic flux in HeLa cells. Loss of <i>Rchy1</i> impaired autophagosome–lysosome fusion and led to the accumulation of amphisomes in larval midgut cells. Similarly, depletion of RCHY1 in HeLa cells disrupted autophagic flux and reduced autolysosome formation, indicating evolutionary conservation of its function. Collectively, our findings identify RCHY1 as a putative regulator of autophagy that facilitates autophagosome-lysosome fusion.</p>

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Ubiquitin ligase RCHY1 regulates autophagosome-lysosome fusion

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月15日

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  • Ruchi Umargamwala,
  • Jantina Manning,
  • Julian M. Carosi,
  • Donna Denton,
  • Sharad Kumar

摘要

Autophagy is a fundamental cellular recycling process that maintains homeostasis during animal development and under nutrient-limiting conditions. In our previous work, we employed autophagy-dependent cell death (ADCD) in the obsolete Drosophila larval midgut as a model to identify the enzymes involved in protein modification via ubiquitination with potential roles in autophagy regulation. From a genetic screen we identified RING E3 ligase RCHY1 as a candidate regulator. Here, we demonstrate that RCHY1 is essential for autophagy regulation during larval midgut ADCD in Drosophila and promotes autophagic flux in HeLa cells. Loss of Rchy1 impaired autophagosome–lysosome fusion and led to the accumulation of amphisomes in larval midgut cells. Similarly, depletion of RCHY1 in HeLa cells disrupted autophagic flux and reduced autolysosome formation, indicating evolutionary conservation of its function. Collectively, our findings identify RCHY1 as a putative regulator of autophagy that facilitates autophagosome-lysosome fusion.