Gryllus Field Crickets as a Novel Model System for Selective Muscle Breakdown and Maintenance

Incidences of sarcopenia, cachexia, and other muscle-wasting disorders are increasing, and occur via elevated protein breakdown and decreased protein synthesis, regulated by interactions between autophagy and mTOR signaling. Established animal models of muscle breakdown are focused on pathological pathways, leaving a gap in our understanding of how animals naturally regulate muscle remodeling. Field crickets rapidly break down the dorsolongitudinal (DLM) flight muscles after completing a dispersal flight, while preserving the neighboring dorsoventral (DVM) muscles. Our research objective is to establish the cricket as a model system for understanding the processes leading to the breakdown and maintenance of skeletal-like muscles in a healthy animal, and to discover how the organism is protected from oxidative stress resulting from massive iron release during muscle breakdown. We hypothesized that autophagy and mitophagy regulate muscle remodeling while mTOR protects neighboring muscles from unwarranted breakdown. Furthermore, we hypothesized that iron buffering is necessary to avoid pathological consequences of rapid muscle breakdown, including oxidative stress from Fenton reactions and ferroptosis. We evaluated muscle organization using transmission electron microscopy, utilized quantitative PCR for gene expression, and measured mitochondrial respiration using an Oroboros O2K microrespirometer to characterize structural and functional changes during non-pathological muscle breakdown. Autophagosomes are formed during muscle breakdown, and beclin, a regulator of autophagy, is upregulated in the DLM muscle before the onset of muscle breakdown. The knock-down of beclin expression using RNA interference delays muscle breakdown. During muscle breakdown in the DLMs, a decline in mitochondrial volume and respiration and increases in drp1 implicate mitophagy. The DVM remains functional during this process, with a much smaller mitochondrial volume and respiration decrease than in the DLM. mTOR is up-regulated in the DVM muscle, consistent with a protective function. Measurement of free iron confirmed that iron is released during muscle breakdown, but no oxidative stress was detected in neighboring muscles. Up-regulation of iron transporters prior to muscle breakdown suggests that crickets avoid oxidative damage from massive iron release during muscle breakdown by modifying iron handling. Understanding how skeletal-like muscles are targeted for breakdown and protected in healthy animals as a normal part of the lifecycle will advance our understanding of the underlying molecular mechanisms and establish new therapeutic targets to improve human muscle homeostasis. 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 2025 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.