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Mitochondrial dysfunction or morphological abnormalities in human pathogenic fungi are known to contribute to azole resistance; however, the underlying molecular mechanisms are unknown. In this study, we investigated the link between mitochondrial morphology and azole resistance in <i>Candida glabrata</i>, which is the second most common cause of human candidiasis worldwide. The ER-mitochondrial encounter structure (ERMES) complex is thought to play an important role in the mitochondrial dynamics necessary for mitochondria to maintain their function. Of the five components of the ERMES complex, deletion of <i>GEM1</i> increased azole resistance. Gem1 is a GTPase that regulates the ERMES complex activity. Point mutations in <i>GEM1</i> GTPase domains were sufficient to confer azole resistance. The cells lacking <i>GEM1</i> displayed abnormalities in mitochondrial morphology, increased mtROS levels, and increased expression of azole drug efflux pumps encoded by <i>CDR1</i> and <i>CDR2</i>. Interestingly, treatment with N-acetylcysteine (NAC), an antioxidant, reduced ROS production and the expression of <i>CDR1</i> in Δ<i>gem1</i> cells. Altogether, the absence of Gem1 activity caused an increase in mitochondrial ROS concentration, leading to Pdr1-dependent upregulation of the drug efflux pump Cdr1, resulting in azole resistance.