Mitochondrial Dysfunction and Endoplasmic Reticulum Stress in Chronic Pain

Mitochondrial-endoplasmic reticulum interactions in lung diseases.

The pathogenesis of lung diseases is highly complex and multifactorial, posing a persistent challenge to global public health, while effective therapeutic options remain limited. Therefore, systematically elucidating the cellular and molecular mechanisms underlying lung injury is a crucial prerequisite for developing novel therapeutic strategies. Accumulating evidence highlights that the endoplasmic reticulum and mitochondria are key organelles driving the progression of lung injury. Notably, mitochondria-associated membranes (MAMs) form a structural and functional bridge between the endoplasmic reticulum and mitochondria, highlighting the essential role of inter-organellar communication in maintaining lung function homeostasis. This review comprehensively summarizes the autonomous mechanisms of the mitochondria and endoplasmic reticulum in lung injury-related diseases, with a further focus on the complex architecture and regulatory mechanisms of MAMs. It emphasizes the molecular mechanisms by which dysfunctional MAMs contribute to the onset and progression of lung injury, including Ca²⁺ signaling, oxidative stress, lipid synthesis and transport, UPRER and UPRmt, mitochondrial homeostasis, and cell death. Finally, incorporating recent research advances, we discuss the current challenges and future prospects in this field, with particular emphasis on intervention strategies targeting Ca²⁺ transport at MAMs, mitochondrial quality control, endoplasmic reticulum stress, and metabolic coupling, as well as their potential for clinical translation. Overall, a deeper understanding of the functional interaction network among mitochondria, the endoplasmic reticulum, and their associated MAMs is expected to provide a robust theoretical foundation and translational insights for elucidating novel molecular mechanisms underlying lung injury and optimizing therapeutic strategies.

Targeting mitochondrial dysfunction with traditional Chinese medicine for inflammatory bowel disease: a comprehensive review

Inflammatory Bowel Disease (IBD) is a chronic relapsing inflammatory condition of the intestine, characterized by symptoms such as chronic diarrhea, abdominal pain, and weight loss. The pathogenesis of IBD is complex, with mitochondrial dysfunction being considered a key factor in its onset, progression, and persistence. Mitochondria, as the primary energy suppliers within cells, not only produce adenosine triphosphate (ATP) but also play crucial roles in regulating cellular metabolism, maintaining redox balance, and controlling cell death processes. Targeting mitochondria to regulate mitochondrial functions, including energy metabolism, oxidative stress, mitophagy, dynamics, and biogenesis, as well as maintaining the dynamic balance of the “gut microbiota-mitochondria axis,” has emerged as a promising strategy for the prevention and treatment of IBD. Traditional Chinese Medicine (TCM) has shown potential multi-target regulatory properties in preclinical studies; however, robust clinical validation and target-specific pharmacological evidence remain limited. This review explores the mechanisms and underlying connections between mitochondrial dysfunction and IBD, summarizing the current research on how active metabolites of TCM modulate mitochondrial dysfunction in the prevention and treatment of IBD. It provides new insights into the pathogenesis of the disease and opens up new avenues and strategies for the prevention, treatment, and research on IBD treatment with TCM.

Implication of Proteostasis Impairment and Endoplasmic Reticulum Stress in Age-Related Neurodegeneration

Mitochondrial quality control in health and disease: mechanisms and therapeutic targets

Mitochondria are essential for cellular homeostasis, integrating various signals to control key cellular functions such as metabolism, apoptosis, inflammation, cell proliferation and redox balance. Given their multifaceted functions, it is not surprising that mitochondrial dysfunction has been implicated as a key contributor to the pathogenesis of numerous human diseases. Consequently, preserving mitochondrial integrity and functionality is vital for overall organismal health. Mitochondrial health is safeguarded by a sophisticated and tightly regulated network of quality control systems. These include mitochondrial proteostasis, which ensures proper protein folding and degradation; mitochondrial biogenesis, which governs the synthesis of new mitochondria; mitochondrial dynamics, encompassing fusion and fission processes; and mitophagy, the selective autophagic removal of damaged mitochondria. Additionally, these core systems are intricately connected to other crucial mitochondrial processes, such as the maintenance of mitochondrial DNA integrity, the regulation of cristae architecture, and the control of mitochondrial permeability transition, all of which are indispensable for optimal mitochondrial performance. Preclinical and clinical studies consistently demonstrate a strong link between impairments in these quality control mechanisms and both aging and the development of a wide spectrum of diseases. These include cancer, metabolic disorders, cardiovascular conditions, neurodegenerative diseases and autoimmune pathologies. In this review, we explore the different facets of mitochondrial quality control and discuss their implications in disease progression and aging. Furthermore, we highlight recent advances in interventions and therapies aimed at modulating mitochondrial quality control, providing an overview of their potential to mitigate disease burden and promote healthy aging.

ER–mitochondria contact sites and organelle stress in asthma

Exercise as a Programmable Regulator of Mitophagy Sensitivity in Aging Muscle and Age-Related Disease.

Aging is increasingly recognized as a systems-level process marked by progressive deterioration of mitochondrial performance in tissues with high energetic demand, placing skeletal muscle at the center of systemic metabolic and functional decline. Beyond its mechanical role, skeletal muscle acts as a regulatory hub for energy homeostasis, redox balance, and inter-organ signaling, functions that depend critically on effective mitochondrial quality control. Emerging evidence indicates that age-related mitochondrial dysfunction arises not only from impaired biogenesis but also from dysregulated mitophagy, the selective autophagic removal of damaged mitochondria. Mitophagy is now understood as a dynamic, context-sensitive process integrating metabolic state, mechanical loading, and cellular stress, rather than a binary response to severe mitochondrial damage. Exercise represents a uniquely potent, non-pharmacological modulator of this process. By transiently perturbing cellular energy balance, calcium flux, and redox signaling, physical activity activates coordinated mitophagic and biogenic programs that promote mitochondrial renewal without precipitating energetic collapse. In contrast to chronic pathological stressors, exercise induces pulsatile, recoverable mitochondrial challenges that recalibrate quality-control thresholds. Importantly, mitophagic responses to exercise are heterogeneous and nonlinear. Exercise modality, intensity, frequency, and temporal organization generate distinct mitochondrial signals, producing fiber-type-specific and age-dependent adaptations. In aging muscle, elevated activation thresholds, delayed clearance kinetics, and lysosomal constraints frequently blunt adaptive mitophagy, indicating remodeling rather than a simple suppression of quality-control logic. This review integrates molecular, physiological, and translational evidence to redefine exercise as a precision regulator of mitophagy in aging skeletal muscle. This review proposes that tailored exercise strategies targeting mitophagy may provide a scalable, non-pharmacological approach to preserve mitochondrial quality and functional resilience during aging.