2026-07-10 | Research progress on VDAC2 in mitochondrial dysfunction-related diseases.
Mitochondrial dysfunction contributes to numerous human diseases. Voltage‑dependent anion channel 2 (VDAC2) is an essential outer mitochondrial membrane porin with distinct structural and functional properties that are non-redundant with those of VDAC1 and VDAC3. VDAC2 precisely controls ATP, ADP, NADPH and Ca2+ transport, thereby acting as a key hub for energy metabolism, calcium homeostasis, redox balance and cell fate. It directly binds BAX/BAK to differentially regulate apoptosis and is also involved in ferroptosis, necroptosis, Parkin‑dependent mitophagy, and lipid transport through protein interactions and post‑translational modifications. Aberrant expression or dysfunction of VDAC2 promotes tumorigenesis, neurodegenerative diseases, and cardiovascular disorders through metabolic reprogramming, apoptotic imbalance, immune evasion, and impaired mitochondrial quality control. Several small‑molecule compounds and peptides targeting VDAC2 have been developed, providing valuable tools for mechanistic studies and potential therapies for mitochondrial dysfunction‑related diseases. Several major challenges remain, including poor isoform selectivity, a lack of tissue‑specific conditional knockout models, and unclear cross‑species conservation. This review systematically summarizes the structure of VDAC2, its versatile roles in mitochondrial function, disease mechanisms, and advances in pharmacological targeting. We also highlight current limitations and future directions, with the aim of providing a theoretical basis for VDAC2‑targeted drug development and clinical translation.
Open article ↗
2026-07-07 | Mitochondria setting the stage for ferroptosis.
Ferroptosis is an iron-dependent form of regulated cell death driven by lipid peroxidation. Recent advances challenge the view of ferroptosis as a predominantly cytosolic process and instead position mitochondria as central regulators of ferroptosis by coordinating iron metabolism, lipid composition, and redox homoeostasis. This review discusses ferroptosis from a mitochondrial perspective and examines its potential relevance to primary mitochondrial diseases, where defects in oxidative phosphorylation profoundly remodel cellular metabolism and redox homoeostasis. The review highlights emerging roles for mitochondrial iron-sulfur cluster biogenesis, coenzyme Q metabolism and trafficking, mitochondrial lipid remodelling, and stress-response signalling in shaping ferroptotic vulnerability. Finally, we discuss current evidence linking ferroptosis to mitochondrial pathology and the therapeutic opportunities arising from targeting ferroptosis pathways in mitochondrial disease.
Open article ↗
2026-07-07 | COQ2-Associated Primary Coenzyme Q10 Deficiency Presenting With Proteinuria: A Case Report and Literature Review.
Primary coenzyme Q10 (CoQ10) deficiency (PCOQ10D) is an autosomal recessive mitochondrial disorder caused by pathogenic variants in genes involved in the CoQ10 biosynthetic pathway, including PDSS2, COQ2, COQ6, and COQ8B/ADCK4. Among these, pathogenic variants in the COQ2 gene impair oxidative phosphorylation and mitochondrial biogenesis in podocytes, often leading to encephalopathy and nephropathy. Clinical data were collected from a pediatric patient with proteinuria caused by COQ2 gene variants, who was admitted to the Children's Hospital Affiliated to Nanjing Medical University in June 2025. Relevant examinations were completed, and whole-exome sequencing (WES) was performed to screen for potential genetic variants in the patient's genomic DNA. Pathogenicity assessment of the identified variants was conducted in accordance with the American College of Medical Genetics and Genomics (ACMG) guidelines and online bioinformatics tools. Additionally, a systematic literature review on COQ2-associated nephropathy was carried out in this study. The patient initially presented with global developmental delay accompanied by neurological lesions and developed proteinuria at 6 months of age. Genetic testing revealed two pathogenic variants: c.368G>A, p.(Arg123His) and c.908A>G, p.(Tyr303Cys). After oral administration of high-dose CoQ10 (85 mg/kg/d) combined with enalapril maleate (0.80 mL/kg/d), the patient achieved complete remission of proteinuria and maintained stable renal function. PCOQ10D exhibits marked phenotypic heterogeneity, characterized by variations in age of onset, organ involvement, and clinical severity, as well as significant interindividual differences in treatment responses to CoQ10 supplementation. This case expands the phenotypic spectrum of the disease. Moreover, the therapeutic outcomes suggest that all diagnosed patients require long-term supplementation with adequate doses of CoQ10, which is of great significance for delaying disease progression.
Open article ↗
