VDAC1: The mitochondrial gatekeeper in the battle against hearing loss (Review)

The development of hearing loss is strongly associated with mitochondrial damage, particularly downstream of mitochondrial autophagy, which is a process that is coincidentally key for selectively removing damaged mitochondria. Voltage-dependent anion channel 1 (VDAC1) is an important protein in the mitochondrial outer membrane that regulates various essential biological processes, including energy metabolism, calcium ion transport and cell apoptosis. VDAC1 can bidirectionally regulate cell fate, where its oligomerization can exacerbate oxidative stress, leading to cell damage and even death. By contrast, its ubiquitination supports cell survival by regulating mitochondrial autophagy, thereby improving mitochondrial quality control. VDAC1 can significantly contribute to the prevention and management of hearing loss. The present review summarizes how the ubiquitination and oligomerization modifications of VDAC1 can balance cell survival and death, while also exploring current hypotheses on mechanisms associated with hearing loss. These findings emphasize the research prospects of VDAC1 as a novel target for hearing loss treatment.