SUMO protease Pira induces autophagy-related cell death during <i>Drosophila</i> development

Autophagy is a major intracellular degradative process required for maintaining homeostasis in multicellular organisms. Aberrant autophagy is considered to induce internal environmental disturbance and cell death. Therefore, it is of great significance to explore the regulatory mechanism of autophagy. Here, we report a positive role of protein Pira, a SUMO protease, in inducing autophagy and autophagy-dependent cell death during Drosophila development. We found that overexpression of pira in wing imaginal discs was able to induce selective autophagy (mitophagy) and autophagic cell death, resulting in wing loss. Moreover, Pira-induced mitophagy and cell death were dependent on the accumulation of Sima, the sole Drosophila homolog of mammalian HIF-1α. Disrupting the sima expression was adequate to inhibit the Pira effects for cell survival and wing development. In addition, the biomarkers of aging were activated in wing discs upon pira overexpression, and excessive Pira shortened fly lifespan, suggesting that Pira may be associated with aging. Together, we provided evidence demonstrating that ectopic Pira can activate the Sima/HIF-1α-mediated mitophagy and cell death, thereby leading to developmental defects in Drosophila.