Mitochondrial Stress and Mitokines: Therapeutic Perspectives for the Treatment of Metabolic Diseases

Abstract

Mitochondrial stress and the dysregulated mitochondrial unfolded protein response (UPR<sup>mt</sup>) are linked to various diseases, including metabolic disorders, neurodegenerative diseases, and cancer. Mitokines, signaling molecules released by mitochondrial stress response and UPR<sup>mt</sup>, are crucial mediators of inter-organ communication and influence systemic metabolic and physiological processes. In this review, we provide a comprehensive overview of mitokines, including their regulation by exercise and lifestyle interventions and their implications for various diseases. The endocrine actions of mitokines related to mitochondrial stress and adaptations are highlighted, specifically the broad functions of fibroblast growth factor 21 and growth differentiation factor 15, as well as their specific actions in regulating inter-tissue communication and metabolic homeostasis. Finally, we discuss the potential of physiological and genetic interventions to reduce the hazards associated with dysregulated mitokine signaling and preserve an equilibrium in mitochondrial stress-induced responses. This review provides valuable insights into the mechanisms underlying mitochondrial regulation of health and disease by exploring mitokine interactions and their regulation, which will facilitate the development of targeted therapies and personalized interventions to improve health outcomes and quality of life.