| Summary: | <i>Candida albicans</i> is one of the most common opportunistic fungal pathogens in human beings. When infecting host cells, <i>C. albicans</i> is often exposed to oxidative stress from the host immune defense system. Maintenance of mitochondrial and vacuolar functions is crucial for its resistance to oxidative stress. However, the role of vacuole and mitochondria patchs (vCLAMPs) in cellular oxidative stress resistance and in the maintenance of organelle functions remains to be elucidated. Herein, the function of the vCLAMP protein Vam6 in response to oxidative stress was explored. The results showed that the <i>vam6</i>∆/∆ mutant exhibited obvious mitochondrial swelling, mtDNA damage, reduced activity of antioxidant enzymes, and abnormal vacuolar morphology under H<sub>2</sub>O<sub>2</sub> treatment, indicating its important role in maintaining the structures and functions of both mitochondria and vacuoles under oxidative stress. Further studies showed that deletion of <i>VAM6</i> attenuated hyphal development under oxidative stress. Moreover, loss of Vam6 obviously affected host tissue invasion and virulence of <i>C. albicans</i>. Taken together, this paper reveals the critical role of vCLAMPs in response to oxidative stress in <i>C. albicans</i>.
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