This review systematically summarizes the structure of VDAC2, its versatile roles in mitochondrial function, disease mechanisms, and advances in pharmacological targeting, with the aim of providing a theoretical basis for VDAC2‑targeted drug development and clinical translation.
Recent studies demonstrate promising therapeutic targets for mitochondrial dysfunction and highlight the need for research in mitochondrial function to change the therapeutic landscape in the management of mitochondrial dysfunction-associated diseases.
Olufemi Akintayo Akinkunmi, Feyikemi Funmilayo Araba, J. A. Chukwudebelu et al.· Frontiers in Cell and Develo...· 0 citations
This review systematically summarize the specific mitochondrial pathological phenotypes in various diseases and provides a comprehensive overview of natural products that correspond to these phenotypes, along with their mechanisms of action.
Xinyue Liu, Hu Li, Xuekai Wang et al.· Chinese Journal of Natural M...· 0 citations
The different facets of mitochondrial quality control are explored and their implications in disease progression and aging are discussed, providing an overview of their potential to mitigate disease burden and promote healthy aging.
Agustina Creus, Shrestha Mohapatra, Leonardo Ortega et al.· Signal Transduction and Targ...· 2 citations
Oxidative stress and mitochondrial dysfunction were intimately linked processes driving aging and numerous human diseases. Mitochondria generating reactive oxygen species (ROS) during energy metabolism; physiological ROS levels are vital for cell signaling and adaptation. However, excessive ROS damage mitochondrial DNA (mtDNA), respiratory proteins, and membrane lipids, reducing ATP production, disturbing calcium balance, and impairing organelle function. In turn, damaged mitochondria produce more ROS and release mtDNA, activating inflammatory pathways such as cGAS-STING and NLRP3. Mitochondrial quality control mechanisms—fusion, fission, mitophagy, proteostasis, and PGC-1α-driven biogenesis—are essential for homeostasis. This review discusses the biochemical links between oxidative stress and mitochondrial dysfunction and their roles in cardiovascular disease, type 2 diabetes, neurodegeneration, metabolic liver disease, cancer, and aging. We summarize widely used biomarkers (F2-isoprostanes, oxidized nucleic acids, mitochondrial respiration, multi-omics) and current therapeutic strategies, including exercise-induced mitohormesis, NRF2 activation, mitochondria-targeted antioxidants (MitoQ), cardiolipin-targeting peptides (elamipretide), NAD⁺ restoration, and mitophagy enhancers (urolithin A). Although several approaches show biological promise, clinical outcomes remain variable. Future therapies must prioritize restoring mitochondrial quality and redox balance over simplistic ROS scavenging.
A. Abdulkader, A. M. Hussein· World Journal of Chemical an...· 0 citations
DJ-1 is a redox-sensitive protein implicated in early-onset Parkinson’s disease, and its mitochondrial localization protects against oxidative stress, but the mechanisms regulating its submitochondrial targeting and functional impact on mitochondrial integrity remain poorly understood. We identify voltage-dependent anion channel 1 (VDAC1) as a regulator of the submitochondrial distribution of DJ-1 during stress. Endogenous DJ-1 interacted with VDAC1, and loss of VDAC1 reduced stress-induced DJ-1 accumulation within the mitochondrial matrix. VDAC1-deficient neurons exhibited mitochondrial fragmentation, impaired oxidative phosphorylation, reduced ATP levels, altered reactive oxygen species (ROS) responses, and increased sensitivity to MPP⁺. Matrix-targeted, but not outer-membrane-targeted, DJ-1 rescued basal, ATP-linked, and maximal respiration, improved mitochondrial morphology, and enhanced neuronal survival. ATP synthase inhibition also rapidly increased mitochondrial DJ-1, suggesting bioenergetic stress promotes its mitochondrial accumulation. Our findings identify compartment-specific localization as a key determinant of DJ-1 function and establish VDAC1-dependent matrix targeting as a critical mechanism supporting mitochondrial integrity during stress.
Jéssica Taday, D. Im, S. Hewitt et al.· bioRxiv· 0 citations
Mitochondria integrate metabolic, signalling, and quality-control pathways that are critical for neuronal and glial homeostasis. Beyond ATP production, they regulate redox balance, calcium dynamics, proteostasis, innate immune signalling, and the molecular pathways governing cell survival and death. This Closing Editorial synthesizes the main advances reported in this Collection across neurodegeneration, neurodevelopmental vulnerability, inherited mitochondrial disorders, neurotrauma, drug-induced neurotoxicity, and neuroimmune regulation. Collectively, these studies establish mitochondrial dysfunction as a heterogeneous and context-dependent process rather than a uniform or secondary consequence of neurological disease. Mitochondrial alterations are dynamically regulated across cell types, subcellular compartments, and disease stages, and are tightly coupled to inter-organelle communication and cellular stress-response pathways. The contributions highlight convergent mechanisms linking astrocytic mitochondrial DNA damage, dysregulated RNA-binding proteins, altered mitochondria–endoplasmic reticulum contacts, disrupted iron and redox homeostasis, and mitochondrial–inflammatory signalling to neuronal vulnerability and impaired circuit integrity. They also identify potential therapeutic targets while defining key unresolved questions, particularly the need to establish mechanistic causality, delineate cell- and compartment-specific mitochondrial responses, and validate findings using clinically relevant models and outcome measures. Overall, this Collection positions mitochondrial biology as a mechanistic framework connecting metabolic dysfunction, cellular stress, neuroinflammation, and neuronal degeneration, and supports its development as a therapeutic target for disease-modifying interventions in neurological disorders.
Rita Valenzuela, A. I. Rodriguez-Perez· Cellular and molecular neuro...· 0 citations
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