Coordination of iron mobilization and autophagy drives muscle breakdown in crickets

Iron is an essential nutrient for animal life as its chemical properties have given it an indispensable role in cellular processes like energy production. Therefore, iron is important for metabolically costly activities like flight and reproduction, and for the tissues that support these functions (muscles and ovaries). Field crickets break down their dorsolongitudinal (DLM) flight muscle while preserving their neighboring dorsoventral (DVM) muscle after completing dispersal flight and transition to a period of reproduction. This process reduces the metabolic costs of the flight muscle, freeing up energy for reproduction, and can also allow for the repurposing of broken-down nutrients from the muscle to the ovaries to facilitate reproductive development. However, we currently lack an understanding of which nutrients are used and how they are transported to the ovaries. Given iron’s importance in muscle function and reproduction, it is likely that iron homeostasis may act as a critical yet unexplored driver of muscle breakdown and reproductive provisioning. Our research objective is to manipulate autophagy and iron transport to test for a causal linkage between flight muscle breakdown and reproductive provisioning. We hypothesized that co-regulation of autophagy and iron transport during muscle remodeling protect against oxidative stress and ensures efficient iron transport to the ovaries to support oogenesis. Using quantitative PCR, we profiled gene expression patterns in the DLM and the DVM and discovered joint up-regulation of autophagy and iron transport proteins prior to muscle breakdown. We suppressed autophagy by knocking down beclin, a key autophagy initiator, using RNA interference (RNAi) and blocked muscle breakdown, and observed a joint downregulation of iron transport. We then suppressed iron transport using an RNAi knockdown against transferrin and observed a joint-down-regulation of autophagy, demonstrating the co-regulation of these two pathways during muscle breakdown. To confirm that iron is transported from flight muscles to the ovaries, we measured iron and transferrin protein levels in the muscle, hemolymph (blood), and ovaries and found that iron was released from the muscles, increased in the hemolymph concurrent with increases in transferrin protein, and subsequently transferrin protein and iron increased in the ovaries. We induced autophagy pharmacologically using rapamycin and found that muscle breakdown was accelerated, while concurrently iron content was decreased in the muscles and increased in the ovaries. To test if iron transport also protects against oxidative stress, we performed HNE-blots and found no evidence for oxidative damage to the flight muscles, suggesting that crickets avoid oxidative damage during breakdown by using iron transport during autophagy-mediated muscle breakdown. Altogether, this work demonstrates that autophagy and iron transport are co-regulated to ensure protection from oxidative damage and efficient transfer of iron to developing ovaries during muscle breakdown. This work provides insight into the molecular mechanisms that allow for the controlled breakdown and protection of muscles as a natural part of the life cycle. This work has been supported by funding from the National Science Foundation and the University of California, Berkeley. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.