At BPS2023, I had the pleasure to meet Drs. Sonia Cortassa and Miguel A. Aon, and learn about their work on mitochondrial dynamics. One of the key concepts that lie at the center of their research is dynamic regulation (homeodynamics; Lloyd, Aon and Cortassa, 2001), a radical but all-embracing notion that departs from the classical homeostatic paradigm. Here, I wish to provide a brief overview of their contribution to the ongoing development of homeodynamics in physiology as a fundamental concept and discuss in short how such a paradigm shift from homeostasis to homeodynamics would enable us to see health and disease in a new light. 

Tracing back to early 1990s, the work by Drs. Sonia Cortassa and Miguel A. Aon has centered around the questions how mitochondrial activity oscillates over time and what role these oscillations play in physiology. Together with other pioneers, they demonstrated that oscillations in mitochondrial activity (on the sub-minute timescale) regulate glycolysis to coordinate ATP production in yeast culture (Aon et al., 1991) and the cardiomyocyte (Romashko, Marban and O’Rourke, 1998). Further, they showed that mitochondrial oscillations are tightly coupled to produce a synchronized action in cardiac bioenergetics (Aon et al., 2003; Aon, Cortassa and O’Rourke, 2006). An integrated computational model of the tricarboxylic acid (TCA) cycle, oxidative phosphorylation and mitochondrial Ca2+ handling was proposed, validated, and used to perform in silico experiments on a variety of topics till today (Cortassa et al., 2003 & 2006 & 2021). Intriguingly, ultradian rhythms (oscillations with periods shorter than 24 hours) in avian behavior were found to be synchronized through fractal organization across timescales (Guzmán et al., 2017), suggesting the universality of homeodynamics in physiology. 

More recently, their group reported, for the first time, deterministic chaos in mitochondrial functions and characterized the conditions underlying the transition from oscillations to chaos in the mitochondria, in the context of pathological transformations such as the onset of cardiac fibrillation (Kembro et al., 2014 & 2018). These findings made it clear that dynamic regulation of biological systems can play critical roles in determining health and disease, apart from the homeostasis-dominated paradigm that emphasizes equilibrium control. Indeed, examples have also been reported in other systems (reviewed in Xiong & Garfinkel, 2023), in support of the functionality of dynamic regulation in physiology. With emerging technologies to detect and analyze dynamical biological behaviors (Cortassa & Aon, 2022), we might soon be able to explore the full scope of homeodynamics in normal physiology and pathophysiology.