Research Projects

Muscle function and adaptation depend on the precise organization and interplay of subcellular organelles. The dynamic networks formed by mitochondria and the endo-/sarcoplasmic reticulum (ER) are critical in modulating muscle contractile and metabolic properties. Mitochondrial-ER contacts (MERCs) represent specialized membrane contact sites that regulate a host of cellular processes essential for muscle health, including mitochondrial dynamics, calcium signaling, bioenergetics, and cell survival. Although the importance of muscle fiber type composition and mitochondrial dynamics is well established, comparatively little is known about how ER content, architecture, and MERC formation contribute to muscle function and how these factors become dysregulated in disease and aging. Disruptions in organelle organization and MERCs have been implicated in various muscle-related pathologies, such as dystrophy, cardiac hypertrophy, and type II diabetes mellitus. Stress-induced ER dysfunction can impair muscle contraction and promote age-associated mitochondrial defects, underscoring the need to delineate the mechanisms governing muscle-specific ER structure, MERC formation, and mitochondrial network integrity. However, the molecular and developmental underpinnings of ER organization and its communication with mitochondria remain poorly understood. This project will utilize a Drosophila model to systematically investigate the 3D structure and developmental regulation of the ER and MERCs across multiple muscle types. By identifying key regulators of muscle-specific ER organization and examining how these regulators influence mitochondrial network formation and function, this research will shed light on fundamental principles governing muscle biology. Comparative analyses in mouse skeletal and eye muscles will extend these findings, providing insights into conserved and divergent regulatory mechanisms across species. Given the pivotal role of the ER in Ca²⁺ homeostasis, gene transcription, and energy metabolism, understanding how ER configuration and MERCs modulate muscle function holds the promise of informing strategies to maintain or restore muscle health. Ultimately, these studies will advance our understanding of how ER-mitochondrial crosstalk contributes to muscle physiology and pathology. By uncovering the mechanisms that underlie organelle miscommunication and dysfunction, we can pave the way for targeted interventions to prevent or mitigate the progression of muscle-related diseases and age-associated decline in muscle performance.