REVIEW: Pore-Forming VDAC Proteins of the Outer Mitochondrial Membrane: Regulation and Pathophysiological Role

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Natalia V. Belosludtseva^1,2, Mikhail V. Dubinin², Konstantin N. Belosludtsev^2,a*

¹Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, 142290 Pushchino, Moscow Region, Russia

²Mari State University, 424001 Yoshkar-Ola, Mari El, Russia

^* To whom correspondence should be addressed.

Received: April 16, 2024; Revised: May 12, 2024; Accepted: May 27, 2024

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Voltage-dependent anion channels (VDAC1-3) of the outer mitochondrial membrane are a family of pore-forming β-barrel proteins that carry out controlled “filtration” of small molecules and ions between the cytoplasm and mitochondria. Due to the conformational transitions between the closed and open states and interaction with cytoplasmic and mitochondrial proteins, VDACs not only regulate the mitochondrial membrane permeability for major metabolites and ions, but also participate in the control of essential intracellular processes and pathological conditions. This review discusses novel data on the molecular structure, regulatory mechanisms, and pathophysiological role of VDAC proteins, as well as future directions in this area of research.

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KEY WORDS: VDAC, mitochondria, membrane transport, cell death, cancer, diabetes mellitus, neurodegenerative diseases

DOI: 10.1134/S0006297924060075

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