This review critically evaluates whether MAM-related mechanisms contribute to asthma pathogenesis and where the current evidence remains indirect, and distinguishes MAM-specific mechanisms from MAM-adjacent ER or mitochondrial stress responses across different asthma-relevant cell types.
Nutrient overload induces a state of chronic, low-grade inflammation termed metaflammation, which contributes to the development of metabolic disorders, such as type 2 diabetes (T2D) and metabolic dysfunction-associated steatotic liver disease (MASLD). As a nutrient-sensitive organelle, the endoplasmic reticulum (ER) is highly vulnerable to systemic metabolic burden. When its adaptive capacity is exceeded, ER stress (ERS) activates the unfolded protein response (UPR) and drives cellular dysfunction. This review delineates how the canonical UPR sensors transduce metabolic stress into pro-inflammatory signaling cascades. By engaging key transcriptional regulators and inflammasome complexes, these pathways drive the production of inflammatory mediators, including cytokines, chemokines, and bioactive lipids, such as leukotrienes (LTs) and prostaglandins. Subsequently, the review discusses the organ-specific consequences of ERS in the liver, pancreas, adipose tissue, vascular endothelium, and hypothalamus, highlighting how this stress sustains a self-reinforcing cycle of tissue injury and metabolic dysfunction. Emerging therapeutic strategies are also summarized, ranging from broad-spectrum chemical chaperones to precision UPR modulators and organ-targeted delivery systems aimed at disrupting this pathogenic axis and restoring metabolic homeostasis.
B. Wen, Xiaojin Wu, Kaiying Zhang et al.· Pharmacological Research· 0 citations
Current evidence linking mitochondrial dysfunction, ER stress, and ER-mitochondrial crosstalk to the pathogenesis of chronic pain is summarized and their potentials as therapeutic targets are discussed.
A. Yadawa, Sufang Liu, F. Tao· Brain Science· 0 citations
Abstract Sepsis is increasingly viewed as a disorder of inflammatory, metabolic, and mitochondrial homeostasis, but the path from metabolic disturbance to regulated cell death (RCD) and organ injury remains incompletely defined. Human studies show clinically meaningful metabolic and bioenergetic heterogeneity, while experimental models link mitochondrial stress, inflammatory signaling, membrane disruption, and pathway-specific RCD to tissue dysfunction. This review asks how evidence can be moved from co-occurrence toward mechanism. We synthesize findings across systemic metabolic phenotypes, cell-intrinsic immunometabolism, mitochondrial stress, RCD execution, membrane failure, inflammatory cargo release, organ injury, and therapeutic relevance. Apoptosis has the strongest direct human support as a non-lytic route of immune-cell depletion and epithelial loss; pyroptosis, ferroptosis, necroptosis, and PANoptosis are supported mainly by sepsis-relevant models and remain context dependent. Stronger mechanistic inference requires aligned measurements of metabolic flux, mitochondrial state, RCD execution, membrane integrity, extracellular cargo, host-defense effects, and tissue outcomes within matched cellular, organ, model, and temporal contexts. This framework separates association, susceptibility, execution, inflammatory release, tissue consequence, and therapeutic relevance when interpreting links among metabolic stress, mitochondrial stress, and RCD in sepsis.
Guohairong Pan, Lulu Zhou, Ruochong Wang et al.· Journal of Inflammation Rese...· 0 citations
ABSTRACT Apoptosis is a core program regulating organismal homeostasis and plays a pivotal role in the onset and progression of most diseases. Increasing evidence in recent years indicates that mitochondria are not only central to cellular metabolism but also play a pivotal role in regulating apoptosis. However, no systematic review elucidating how mitochondria finely regulate apoptotic processes through multidimensional mechanisms, including apoptosis‐resistant diseases such as cancer. This paper systematically summarizes the molecular mechanisms by which mitochondria mediate apoptosis. We focus on the regulation of cytochrome c (Cyt c) release by the Bcl‐2 protein family and the activation of downstream caspase cascades. Furthermore, we provide an in‐depth analysis of intrinsic factors, including mitochondrial structural remodeling (membrane rupture, cristae remodeling, and membrane lipid redistribution), dynamics imbalance (fusion, fission, and mitophagy), and mitochondrial DNA abnormalities, as well as extrinsic factors involving interorganelle interactions with the endoplasmic reticulum, lysosomes, and other organelles. Additionally, we review clinical and preclinical advances in drugs targeting these pathways. This review aims to provide a comprehensive perspective on the complex network of mitochondrial regulation of apoptosis and offer valuable insights for developing novel clinical therapeutic strategies for cancer and other diseases.
Rubin Tan, Jinming Zhao, Rong Wang et al.· MedComm· 0 citations
This review summarizes the key receptors, regulatory mechanisms, and the latest research on ER-phagy in various inflammation-related diseases, aiming to draw academic attention to the important value of ER-phagy in inflammatory diseases.
Chunxia Wang, Jing Gao, Changsheng Guo et al.· Frontiers in Immunology· 0 citations
Although mtISR has been characterized in primary mitochondrial myopathies, secondary mitochondrial dysfunction in neuromuscular disorders suggests that mtISR-related pathways may also be activated in these conditions, and its roles in skeletal muscle pathology are discussed.
İsra Şinik, Evrim Aksu-Mengeş, B. Balci-Hayta· Bratislava Medical Journal· 0 citations
