Autophagy, a fundamental cellular degradation and recycling process, has emerged as a central regulator of systemic physiology by orchestrating communication between the brain and peripheral organs. Beyond its traditional role in maintaining intracellular homeostasis, autophagy coordinates immune responses, metabolic balance, and inter-organ signaling through mechanisms including selective degradation and secretory pathways. In this review, we explore how autophagy in neurons, glial cells, immune cells, and metabolic tissues modulates both local and systemic functions, impacting processes such as neuroinflammation, energy homeostasis, and gut-brain axis communication. We highlight the dual role of autophagy in promoting tissue health and facilitating the transfer of metabolic and inflammatory cues across organ systems. Additionally, we discuss how autophagy dysfunction disrupts brain-periphery communication, contributing to the development of neurodegenerative and metabolic diseases. Understanding the mechanisms underlying autophagy-dependent inter-organ signaling will help identify therapeutic avenues for restoring systemic homeostasis and prevent the development of chronic diseases.
Sandoval-Valenzuela et al. (Tue,) studied this question.