Vacuole and mitochondria patch (vCLAMP) and ER-mitochondria encounter structure (ERMES) maintain cell survival by

Xiaolong Mao1, Liping Peng2, Li Yang2

  • 1Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Science, Nankai University, Tianjin, 300071, China; School of Laboratory Animal & Shandong Laboratory Animal Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Shandong, 250000, China.

Insights

The vacuole and mitochondria patch (vCLAMP) and ER-mitochondria encounter structure (ERMES) are crucial for Candida albicans survival. Disrupting these structures impairs mitochondrial function and inhibits growth, highlighting them as potential antifungal drug targets.

Area of Science:

  • * Cell biology
  • * Mycology
  • * Molecular biology

Background:

  • * Candida albicans is an opportunistic fungal pathogen causing significant clinical infections.
  • * The emergence of drug-resistant strains necessitates the identification of novel antifungal drug targets.
  • * Vacuole and mitochondria patch (vCLAMP) and ER-mitochondria encounter structure (ERMES) are key membrane contact sites in yeast, but their roles in C. albicans are uncharacterized.

Purpose of the Study:

  • * To investigate the function of vCLAMP and ERMES in maintaining cell survival and mitochondrial integrity in Candida albicans.
  • * To determine the impact of vCLAMP and ERMES disruption on C. albicans growth, mitochondrial function, and morphology.

Main Methods:

  • * Construction of VAM6 and MDM34 knockout mutants (vam6Δ/Δmet-MDM34) using a MET3 promoter-regulated induction system.
  • * Assessment of cell viability using PI-positive assays.
  • * Evaluation of mitochondrial health through analysis of mitochondrial fragmentation, mtDNA damage, ATP levels, and mitochondrial membrane potential.
  • * Observation of filamentous growth inhibition.

Main Results:

  • * Deletion of vCLAMP and ERMES resulted in abnormal growth and impaired cell viability in C. albicans.
  • * The vam6Δ/Δmet-MDM34 mutant displayed significant mitochondrial fragmentation, mtDNA damage, reduced ATP production, and altered mitochondrial membrane potential.
  • * Disruption of vCLAMP and ERMES led to the inhibition of filamentous growth in C. albicans.

Conclusions:

  • * vCLAMP and ERMES play essential roles in maintaining the structural integrity and functional status of mitochondria in C. albicans.
  • * These membrane contact sites are critical for overall cell survival and proper growth of C. albicans.
  • * vCLAMP and ERMES represent promising targets for the development of new antifungal therapies against C. albicans infections.

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