Mitochondrial complex I subunits of Candida albicans are coordinators of biological processes both inside and outside of mitochondria

The mitochondrial ETC complex I (CI) is present in C. albicans and regulation of CI is based on nutrient availability.  Our recent studies indicate that NDH51 (a component of the CI core), NUO1 and NUO2 (two fungal specific- CI proteins), and GOA1 (Candida specific- CI protein), are all required for CI integrity.  Lack of any of these subunits results in an azole hypersensitivity, avirulence, failure of immunity, and a loss of chronological aging. Genomics and proteomics studies reveal that cell membrane synthesis and wall assembly in this organism are regulated in tandem with CI nDNA genes but not mtDNA-encoded genes. When synthesis of CI subunits, phospholipid and ergosterol are repressed in three CI mutants, proteins for CIV assembly and the alternative oxidase (AOX2) are upgraded. Differential proteins of mutants suggest that NUO1 participates in nucleotide synthesis, ribosomal biogenesis and negatively regulates mitochondrial ribosomal biogenesis.  NUO2 plays a redundant but minor role in these cellular processes; however, vesicular trafficking and negatively regulated CI assembly via inhibition of CIA30 are more NUO2–specific. GOA1, on the other hand, appears to regulate membrane transport, to provide protection against mitochondrial ROS and to balance TCA intermediate flow between mitochondria and the cytoplasm.