Targeting Mitochondrial Dysfunction: New Horizons in Drug Discovery for Chronic Disease

Mitochondrial dysfunction is increasingly recognised as a central driver of a broad spectrum of chronic diseases, including neurodegeneration, cardiovascular disease, metabolic disorders, and cancer. Beyond their role in energy production, mitochondria act as critical regulators of oxidative stress, apoptosis, calcium homeostasis, and inflammatory signalling — making them compelling and multifaceted targets for pharmacological intervention.Despite growing mechanistic insight, the translation of this knowledge into effective therapeutic agents remains a significant challenge. Key questions persist around how to selectively modulate mitochondrial targets — such as the electron transport chain complexes, mitochondrial permeability transition pore (mPTP), PINK1/Parkin pathway, and reactive oxygen species (ROS) signalling — without compromising mitochondrial integrity or inducing off-target toxicity.This Research Topic invites original research, reviews, and methods articles that advance the pharmacological targeting of mitochondrial dysfunction in the context of chronic disease. We welcome submissions addressing:Identification and validation of novel mitochondrial drug targetsMechanisms of action of small molecules, peptides, or biopharmaceuticals acting on mitochondrial pathwaysDrug-biomolecule interactions at the level of mitochondrial enzymes, transporters, or membrane channelsPharmacokinetics, metabolism, and toxicology of mitochondria-targeted investigational compoundsLead optimisation and medicinal chemistry strategies for mitochondria-directed therapeuticsMolecular and cellular pharmacology of mitochondrial dynamics (fission, fusion, mitophagy) in disease modelsStudies focused on crude natural extracts without chemical characterisation, purely in silico approaches without experimental validation, and clinical trials are outside the scope of this collection. Topic editors: Nadezda Apostolova, Satyam Kumar Agrawal, Madhunika Agrawal Source: https://www.frontiersin.org/research-topics/79737/targeting-mitochondrial-dysfunction-new-horizons-in-drug-discovery-for-chronic-disease