From cellular balance to clinical breakthroughs: a comprehensive review of ROS homeostasis

Reactive oxygen species (ROS) homeostasis is an essential process that enables cells dynamically regulate their ROS levels, thereby ensuring survival and the execution of diverse physiological functions. Led by Hong-hao Zhou (Academician of Chinese Academy of Engineering), this review provides an in-depth overview of the core principles of ROS homeostasis and discusses its biological significance and potential clinical applications across molecular mechanisms, cell-fate regulation, and pathophysiology. The review was recently published in Molecular Biomedicine, offering a framework for understanding intracellular ROS homeostasis and for exploring advanced therapeutic strategies.

Reactive oxygen species (ROS) are critical regulators of cellular health, acting as both signaling molecules and potential toxins. Their balanced state, known as ROS homeostasis, is crucial for processes like metabolism, growth, and cell survival. This equilibrium is maintained through self-regulatory mechanisms and coordinated organelle interactions. However, any disruption to ROS homeostasis can impair physiological functions and contribute to various diseases throughout an organism's lifespan.

Despite the markedly impact of ROS dysregulation on disease pathogenesis, the precise mechanisms involved and the full therapeutic potential of targeting ROS homeostasis have not been systematically understood. This review provides a comprehensive overview of the diverse roles of ROS and their metabolic associations. It offers an in-depth discussion of the regulatory mechanisms underlying ROS homeostasis and their influence on processes such as cellular metabolism, cell death, and cell survival. By modulating cell fate, ROS play a broad and integral role in the pathogenesis of various diseases. Finally, this review systematically summarizes therapeutic interventions targeting ROS homeostasis.

Key highlights from the study include:

1. ROS homeostasis, driven by distinct ROS species as central regulators, is maintained from early development through self-regulatory mechanisms that keep cellular and tissue ROS in dynamic equilibrium.

2. Intracellular ROS homeostasis is sustained by endogenous and exogenous inputs and involves coordinated regulation across organelles and signaling pathways.

3. ROS homeostasis directly shapes metabolism, growth, differentiation, and cell death.

4. Dysregulation of ROS is a common pathogenic mechanism driving the development of multiple diseases.

5. Therapeutic strategies that modulate ROS homeostasis have substantial clinical value, elucidating disease mechanisms, accelerating drug development, and advancing personalized medicine.

Clinical Implications and Therapeutic Prospects

The review highlights that dysregulation of ROS homeostasis is a common pathogenic mechanism across numerous diseases. By understanding these complex roles, particularly how ROS modulate cell fate, this work provides essential insights for future therapeutic advancements. It systematically summarizes current and emerging therapeutic interventions that target ROS homeostasis, aiming to bridge the gap between basic research and clinical application for a wide range of diseases.

Future Directions

The review highlights the imperative for further investigation into ROS homeostasis across diverse physiological and pathological contexts to deepen the understanding of its dual nature as both critical signaling molecules and potential toxic agents. The authors call for a greater emphasis on its modulation to address broad clinical challenges and for more translational research to bridge basic findings and clinical application. This includes evaluating emerging ROS-modulating strategies as adjuncts to standard therapies, with the hope that their work will catalyze further exploratory and application-oriented studies to refine and optimize treatment strategies across various diseases.

Academician Honghao Zhou and his team hope their work will catalyze further exploratory and application-oriented studies that refine and optimize treatment strategies across diseases.

See the article:

ROS homeostasis in cell fate, pathophysiology, and therapeutic interventions

https://doi.org/10.1186/s43556-025-00338-8