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Using Live Cell STED Imaging to Visualize Mitochondrial Inner Membrane Ultrastructure in Neuronal Cell Models

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Research progress on VDAC2 in mitochondrial dysfunction-related diseases.

Miao Wang^1,2, Yuanyuan Cui^2,3, Yili Sun^4,5

¹School of Pharmacy, Shandong Medical And Pharmaceutical University, Yantai, 264003, China.

Molecular Biology Reports

|July 10, 2026

Summary

Voltage-dependent anion channel 2 (VDAC2) is crucial for mitochondrial function and linked to diseases. Targeting VDAC2 offers therapeutic potential, but challenges in selectivity and research models remain.

Keywords:

Apoptosis Mitochondrial dysfunction Myocardial injury Neurodegenerative diseases Tumor VDAC2

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Area of Science:

Mitochondrial Biology
Molecular Medicine
Biochemistry

Background:

Mitochondrial dysfunction is implicated in various human diseases.
Voltage-dependent anion channel 2 (VDAC2) is a key mitochondrial outer membrane protein.
VDAC2's unique properties are non-redundant with VDAC1 and VDAC3.

Purpose of the Study:

To systematically review VDAC2's structure, function, and role in disease.
To summarize advances in VDAC2-targeted pharmacological strategies.
To highlight limitations and future directions for VDAC2 research and drug development.

Main Methods:

Literature review and systematic summarization of existing research on VDAC2.
Analysis of VDAC2's involvement in cellular processes like energy metabolism, calcium homeostasis, and cell death pathways.
Examination of VDAC2's role in disease pathogenesis and potential therapeutic targeting.

Main Results:

VDAC2 regulates vital transport (ATP, ADP, NADPH, Ca2+), impacting metabolism, redox balance, and cell fate.
VDAC2 interacts with BAX/BAK, influencing apoptosis, and participates in other cell death pathways (ferroptosis, necroptosis, mitophagy).
Aberrant VDAC2 function is linked to tumorigenesis, neurodegeneration, and cardiovascular disorders via metabolic and apoptotic dysregulation.

Conclusions:

VDAC2 is a versatile mitochondrial protein with critical roles in health and disease.
Targeting VDAC2 shows promise for treating mitochondrial dysfunction-related diseases.
Further research is needed to address challenges like isoform selectivity and develop tissue-specific models for VDAC2 drug development.