Mitochondrial VDAC1: A Potential Therapeutic Target of Inflammation-Related Diseases and Clinical Opportunities

Cells. 2022 Oct 10;11(19):3174. doi: 10.3390/cells11193174.


The multifunctional protein, voltage-dependent anion channel 1 (VDAC1), is located on the mitochondrial outer membrane. It is a pivotal protein that maintains mitochondrial function to power cellular bioactivities via energy generation. VDAC1 is involved in regulating energy production, mitochondrial oxidase stress, Ca2+ transportation, substance metabolism, apoptosis, mitochondrial autophagy (mitophagy), and many other functions. VDAC1 malfunction is associated with mitochondrial disorders that affect inflammatory responses, resulting in an up-regulation of the body's defensive response to stress stimulation. Overresponses to inflammation may cause chronic diseases. Mitochondrial DNA (mtDNA) acts as a danger signal that can further trigger native immune system activities after its secretion. VDAC1 mediates the release of mtDNA into the cytoplasm to enhance cytokine levels by activating immune responses. VDAC1 regulates mitochondrial Ca2+ transportation, lipid metabolism and mitophagy, which are involved in inflammation-related disease pathogenesis. Many scientists have suggested approaches to deal with inflammation overresponse issues via specific targeting therapies. Due to the broad functionality of VDAC1, it may become a useful target for therapy in inflammation-related diseases. The mechanisms of VDAC1 and its role in inflammation require further exploration. We comprehensively and systematically summarized the role of VDAC1 in the inflammatory response, and hope that our research will lead to novel therapeutic strategies that target VDAC1 in order to treat inflammation-related disorders.

Keywords: Ca2+; VDAC1; inflammation; metabolism; mitochondria; mitophagy.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cytokines / metabolism
  • DNA, Mitochondrial / genetics
  • DNA, Mitochondrial / metabolism
  • Humans
  • Inflammation / metabolism
  • Mitochondria* / metabolism
  • Oxidoreductases / metabolism
  • Voltage-Dependent Anion Channel 1* / metabolism


  • Cytokines
  • DNA, Mitochondrial
  • VDAC1 protein, human
  • Oxidoreductases
  • Voltage-Dependent Anion Channel 1

Grants and funding

This study was supported by the Foundation of Luzhou Science and Technology Program and Southwest Medical University (NO. 2020LZXNYDJ24 to Xing Wang). Funders had no role in study design, literature collection, review, analyses, interpretation, writing of the report, and so on.