Prolonged Exposure to Microgravity Reduces Cardiac Contractility and Initiates Remodeling in Drosophila

Abstract

Understanding the effects of microgravity on human organs is crucial to exploration of low earth orbit, the moon, and beyond. Drosophila can be sent to space in large numbers to examine the effects of microgravity on heart structure and function, which is fundamentally conserved from flies to humans. Flies reared in microgravity exhibit reduced climbing ability, cardiac constriction with myofibrillar remodeling and diminished output. Isolated heart RNAseq revealed reduced expression of sarcomeric/ECM genes and increased proteasomal gene expression, consistent with a compromised, smaller heart and abnormal proteostasis. This was examined further on a second flight: we found dramatically elevated proteasome aggregates co-localizing with increased amyloid/polyQ deposits. Remarkably, in long-QT causing sei/hERG mutants, proteasomal gene expression at 1g was lower than wildtype, but nevertheless increased, albeit modestly, in microgravity. Therefore, cardiac remodeling and proteostatic stress may be a fundamental response of heart muscle